ARTICLE 1: THE RIGHT IMAGING PROTOCOL FOR THE RIGHT PATIENT
Nandor K. Pinter, MD. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):16–26.
This article provides a high-level overview of the challenge of choosing the right imaging approach for an individual patient. It also presents a generalizable approach that can be applied to practice regardless of specific imaging technologies.
This article constitutes an introduction to the in-depth, topic-focused analyses in the rest of this issue. It examines the broad principles that guide placing a patient on the right diagnostic trajectory, illustrated with real-life examples of current protocol recommendations and cases of advanced imaging techniques, as well as some thought experiments. Thinking about diagnostic imaging strictly in terms of imaging protocols is often inefficient because these protocols can be vague and have numerous variations. Broadly defined protocols may be sufficient, but their successful use often depends largely on the particular circumstances, with special emphasis on the relationship between neurologists and radiologists.
- The American College of Radiology Appropriateness Criteria provide a good starting point for finding the right imaging modality. The American College of Radiology does not prescribe disease-specific protocols.
- Imaging protocols are not generally applicable laws but rather rules that may be adapted to the circumstances.
- Communication is key for two main reasons: (1) the default imaging approach may need to be changed based on relevant clinical data, and (2) communication can facilitate focused examinations and reporting.
- Even if MRI would be the method of choice, in urgent cases CT may be preferred.
- One should always follow the “as low as reasonably achievable” principle with studies that use ionizing radiation.
- Providing MRI safety information for patients with implants improves safety.
- Contrast agents do not automatically make a scan more informative, and clinical gain versus safety risks should always be considered.
- Disease-specific imaging protocols are mostly born out of necessity and refer to a distinct way of manipulating conventional image acquisition or reconstruction in order to produce specific views that highlight pathologic features of the disease. Real disease-specific imaging operates with biomarkers.
- Imaging technologies advance, causing clinical protocols to change. A powerful future technology could rewrite prevailing practices regarding what is considered “right” imaging, or even eliminate the question entirely. This will depend on many factors, an important one being the inertia of the medical industry and practices.
- MRI protocol optimization is the process of creating a disease-specific protocol via iterative customization of imaging sequences. It can provide significant added value, but the process can be lengthy and resource-intensive. The optimization must be driven by clinical outcome and achieved through a systematic approach.
ARTICLE 2: SAFETY CONSIDERATIONS IN MRI AND CT
Robert E. Watson, MD, PhD; Lifeng Yu, PhD. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):27–53.
MRI and CT are indispensable imaging modalities for the evaluation of patients with neurologic disease, and each is particularly well suited to address specific clinical questions. Although both of these imaging modalities have excellent safety profiles in clinical use as a result of concerted and dedicated efforts, each has potential physical and procedural risks that the practitioner should be aware of, which are described in this article.
Recent advancements have been made in understanding and reducing safety risks with MR and CT. The magnetic fields in MRI create risks for dangerous projectile accidents, radiofrequency burns, and deleterious interactions with implanted devices, and serious patient injuries and deaths have occurred. Ionizing radiation in CT may be associated with shorter-term deterministic effects on biological tissues at extremely high doses and longer-term stochastic effects related to mutagenesis and carcinogenesis at low doses. The cancer risk of radiation exposure in diagnostic CT is considered extremely low, and the benefit of an appropriately indicated CT examination far outweighs the potential risk. Continuing major efforts are centered on improving image quality and the diagnostic power of CT while concurrently keeping radiation doses as low as reasonably achievable.
An understanding of these MRI and CT safety issues that are central to contemporary radiology practice is essential for the safe and effective treatment of patients with neurologic disease.
- The three different magnetic fields involved in the creation of MRIs are each associated with defined safety risks.
- The MRI room is one of the most dangerous environments in the hospital.
- The magnet is always “on.” The tremendously powerful magnetic field creates a dangerous projectile risk in the MRI room regardless of whether a patient is being scanned or not.
- Only trained MRI personnel should enter the magnet room in a patient emergency (eg, cardiopulmonary arrest).
- Accurate information about a patient’s implanted devices should be provided to the MRI team with the MRI order.
- Physical spaces related to MRI are defined by a four-zone model. Access to zone III (the technologist control area) and zone IV (the magnet room) is restricted.
- Implanted devices are designated as MR-safe, MR-conditional, or MR-unsafe.
- Well-designed MRI safety systems and procedures must be in place and rigorously followed to prevent serious safety events and accidents involving dangerous projectiles, burns, and unplanned scanning of implanted devices.
- The magnetic fields around the opening of an MRI bore are not uniform; rather, a steep gradient exists in the forces as the magnet is approached.
- Older intracranial aneurysm clips contained ferromagnetic metal, resulting in patient deaths during MRI.
- Heating and burns related to the radiofrequency field are the most common type of MRI safety events.
- Foil-backed medication patches can cause burns during MRI.
- Scanning a patient with an MR-unsafe device or with an MR-conditional device without abiding by the conditions for safe scanning can lead to serious patient injury or death.
- Intrathecal pumps are the type of device associated with the greatest number of patient deaths during MRI in recent years.
- Patients with pacemakers and defibrillators can increasingly be safely scanned if important safety measures are strictly adhered to.
- An insulin pump exposed to MRI is likely unreliable and could lead to serious hyperglycemia or hypoglycemia.
- Displacement of an intraocular ferromagnetic foreign body during MRI can lead to blindness.
- No deleterious clinical effects of gadolinium retention have yet been identified, although continued study of this issue is important.
- Radiation dose in CT is commonly quantified in terms of scanner radiation output, patient absorbed dose, and effective dose.
- Two types of biological effects from radiation exposure in CT occur. One is the deterministic effect (tissue reaction), and the other is the stochastic effect (cancer induction and hereditary effect).
- Deterministic effects rarely occur in diagnostic CT examinations except for some prolonged CT-guided interventional procedures. The risk of radiation exposure in CT refers mostly to stochastic effect.
- At low levels of radiation, considerable uncertainty exists regarding the risk of cancer induction. It was stated in a report by the National Academy of Sciences that at doses of 100 mSv or less, “statistical limitations make it difficult to evaluate cancer risk in humans.”
- It is generally believed that quantitative estimation of cancer risk for an individual patient receiving a radiation dose of less than 100 mSv during CT does not bring clinical value to the patient.
- To maximize the benefit-to-risk ratio, it is still best practice to use the lowest possible radiation dose at each CT examination while generating images with sufficient diagnostic quality. Two basic principles must be followed for managing radiation dose in CT: justification and optimization.
- Commonly used radiation dose–reduction techniques include automatic tube current modulation, automatic tube potential selection, iterative reconstruction, and deep learning–based noise reduction.
- CT operators are required to receive appropriate training on scanner operation, radiation exposure, and emergency procedures.
- The presence of implanted electronic devices should not preclude a clinically justified CT scan. However, to reduce the potential risk of interference between electronic devices and CT radiation, some precautions are needed.
ARTICLE 3: IMAGING OF CENTRAL NERVOUS SYSTEM ISCHEMIA
Julie G. Shulman, MD; Mohamad Abdalkader, MD. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):54–72.
This article describes imaging modalities used in the evaluation of patients presenting with symptoms of acute ischemic stroke.
The year 2015 marked the beginning of a new era in acute stroke care with the widespread adoption of mechanical thrombectomy. Subsequent randomized controlled trials in 2017 and 2018 brought the stroke community even further into this new territory with the expansion of the eligibility window for thrombectomy using imaging-based patient selection, which led to an increase in the use of perfusion imaging. Now, after several years of routine use, the debate is ongoing as to when this additional imaging is truly required and when it results in unnecessary delays in time-sensitive stroke care. At this time, more than ever, a robust understanding of neuroimaging techniques, applications, and interpretation is essential for the practicing neurologist.
CT-based imaging is the first step in most centers for the evaluation of patients presenting with symptoms of acute stroke because of its wide availability, speed, and safety. Noncontrast head CT alone is sufficient for IV thrombolysis decision making. CT angiography is very sensitive for the detection of large-vessel occlusion and can be used reliably to make this determination. Advanced imaging including multiphase CT angiography, CT perfusion, MRI, and MR perfusion can provide additional information useful for therapeutic decision making in specific clinical scenarios. In all cases, it is essential that neuroimaging be performed and interpreted rapidly to allow for timely reperfusion therapy.
- Early ischemic changes evident on noncontrast CT include obscuration of the lentiform nucleus, loss of the gray-white boundary in the insula (insular ribbon sign), and effacement of the cortical sulci (cortical ribbon sign).
- The Alberta Stroke Programme Early CT Score (ASPECTS) is a quantitative assessment of early ischemic changes calculated by visual inspection of 10 specific neuroanatomic regions on noncontrast CT. The maximum score of 10 indicates no evidence of early ischemia.
- The American Heart Association/American Stroke Association guidelines recommend proceeding with mechanical thrombectomy for patients with large-vessel occlusion stroke and an Alberta Stroke Programme Early CT Score (ASPECTS) of 6 or greater who present within 6 hours of last known well time, without additional advanced imaging.
- The posterior-circulation Alberta Stroke Programme Early CT Score (ASPECTS) is a 10-point scale that assesses eight brain regions supplied by the vertebrobasilar system for evidence of early ischemic changes. It has been shown to improve detection of ischemia and predict functional outcome.
- The hyperdense vessel sign can be seen on noncontrast CT and is highly specific for large-vessel occlusion.
- It is recommended to proceed with CT angiography before measuring a serum creatinine level in patients eligible for mechanical thrombectomy without known renal impairment to avoid unnecessary delays in reperfusion.
- CT angiography is extremely accurate for detecting large-vessel occlusion, with sensitivity and specificity of approximately 98%.
- Multiphase CT angiography can be used to obtain a more robust assessment of a patient’s collateral circulation. Quality of collateral flow has been shown to correlate with rate of infarct growth and predict prognosis in some studies.
- CT perfusion uses three parameters to assess a given brain region: cerebral blood flow, cerebral blood volume, and mean transit time. Postprocessing software creates maps based on these measures to approximate the size and location of the infarct core and the ischemic penumbra.
- MRI is more sensitive and specific than CT for the identification of acute stroke and can detect ischemia as early as a few minutes after stroke onset.
- In true restricted diffusion seen in acute ischemic stroke, a region of increased diffusion-weighted imaging signal correlates with a region of low signal intensity on the apparent diffusion coefficient image.
- Diffusion-weighted imaging–negative stroke is rare and most frequently seen in patients with small, posterior-circulation, or hyperacute strokes. Repeat diffusion-weighted imaging is recommended if there is a strong clinical suspicion of ischemia.
- Diffusion-weighted imaging positivity appears within the first few minutes after stroke onset, whereas fluid-attenuated inversion recovery (FLAIR) signal changes take longer to develop. This mismatch has been used to estimate stroke onset and select patients for thrombolysis.
- Acute intraarterial thrombus produces susceptibility artifact and blooming on gradient recalled echo or susceptibility-weighted MRI. This finding is similar to the “hyperdense vessel sign” seen on noncontrast CT and is strongly suggestive of large-vessel occlusion.
- The modified Thrombolysis in Cerebral Infarction scale is used to describe the degree of reperfusion achieved after mechanical thrombectomy. A score of 2b, 2c, or 3 is considered successful reperfusion.
ARTICLE 4: IMAGING OF CENTRAL NERVOUS SYSTEM HEMORRHAGE
Ryan Hakimi, DO, MS, NVS, RPNI, CPB, FNCS, FCCM. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):73–103.
This article aims to familiarize the reader with the various types of nontraumatic central nervous system (CNS) hemorrhage and the various neuroimaging modalities used to help diagnose and manage them.
According to the 2019 Global Burden of Diseases, Injuries, and Risk Factors Study, intraparenchymal hemorrhage accounts for 28% of the global stroke burden. In the United States, hemorrhagic stroke makes up 13% of all strokes. The incidence of intraparenchymal hemorrhage increases substantially with age; thus, despite improvements in blood pressure control through various public health measures, the incidence is not decreasing as the population ages. In fact, in the most recent longitudinal study of aging, autopsy findings showed intraparenchymal hemorrhage and cerebral amyloid angiopathy in 30% to 35% of patients.
Rapid identification of CNS hemorrhage, which includes intraparenchymal hemorrhage, intraventricular hemorrhage, and subarachnoid hemorrhage, requires either head CT or brain MRI. Once hemorrhage is identified on the screening neuroimaging study, the pattern of blood in conjunction with the history and physical examination can guide subsequent neuroimaging, laboratory, and ancillary tests as part of the etiologic assessment. After determination of the cause, the chief aims of the treatment regimen are reducing hemorrhage expansion and preventing subsequent complications such as cytotoxic cerebral edema, brain compression, and obstructive hydrocephalus. In addition, nontraumatic spinal cord hemorrhage will also be briefly discussed.
- Intracranial hemorrhage may be subdivided into spontaneous intraparenchymal hemorrhage, aneurysmal subarachnoid hemorrhage, and intraventricular hemorrhage.
- The pattern of hemorrhage in conjunction with the history and physical examination can guide subsequent neuroimaging, laboratory, and ancillary tests as part of the etiologic assessment.
- Communication about central nervous system hemorrhage noted on head CT should include the type, location, acuity (acute or chronic), volume of the lesion, presence or absence of intraventricular hemorrhage, and extent of cerebral edema and brain compression.
- Compared with head CT, brain MRI has greater sensitivity for the detection of central nervous system hemorrhage, as it identifies both acute and chronic hemorrhages, which are noted as hypointensities on two-dimensional gradient recalled echo (GRE) T2*-weighted imaging and susceptibility-weighted imaging (SWI), or three-dimensional GRE imaging.
- Digital subtraction angiography offers 99% sensitivity and specificity in identifying underlying vascular lesions in cases of central nervous system hemorrhage.
- Transcranial Doppler ultrasonography can predict symptomatic vasospasm and has high sensitivity, specificity, and positive and negative predictive values.
- Head CT angiography with or without venography is recommended in patients without hypertension who are less than 70 years old and present with a lobar intraparenchymal hemorrhage, as one in seven to one in four patients will have an underlying vascular etiology.
- When intraventricular hemorrhage is noted in isolation, digital subtraction angiography and brain MRI are warranted.
- Primary intraparenchymal hemorrhage is most commonly due to arteriosclerosis.
- Hemorrhage volume is calculated using the ABC/2 method.
- When using 0.5-cm slice thickness, the volume of the central nervous system hemorrhage is calculated by multiplying A, B, and C and dividing by 4.
- One-third of patients with intraparenchymal hemorrhage will have hemorrhage expansion within 3 hours of the index scan.
- Head CT angiography immediately after the noncontrast head CT can allow for quick identification of patients at high risk for rapid hemorrhage expansion when the spot sign is noted.
- The ICH Score is a standard communication tool for describing the patient’s clinical condition and is used to document the patient’s extent of illness for purposes of quality assurance and mortality risk stratification.
- The 2022 American Heart Association/American Stroke Association guidelines recommend that the ICH Score not be used in isolation as the basis for limiting life-sustaining measures.
- Cerebral amyloid angiopathy is the most common secondary cause of intraparenchymal hemorrhage.
- For diagnosing cerebral amyloid angiopathy, brain MRI is most revealing, with cortical microhemorrhages and superficial siderosis noted on SWI or T2* sequences.
- The risk of recurrent hemorrhage is higher in patients with central nervous system hemorrhage with underlying cerebral amyloid angiopathy (7.39% per year) than in those with central nervous system hemorrhage due to other causes (1.1% per year).
- Besides a ruptured aneurysm, other etiologies of subarachnoid hemorrhage include arteriovenous malformation, fistula, intracranial dissection, cerebral venous sinus thrombosis, reversible cerebral vasoconstriction syndrome, vasculitis, use of antithrombotic or sympathomimetic drugs, and to a lesser degree uncontrolled hypertension.
- The clinical neurologic examination and the extent of hemorrhage in patients with subarachnoid hemorrhage are communicated and documented using the Hunt and Hess scale and the modified Fisher scale, respectively.
- Advances in SWI sequences now provide a useful adjunct in ruling out subarachnoid hemorrhage in patients whose clinical history is consistent with an aneurysmal subarachnoid hemorrhage but whose head CT and head and neck CT angiography are normal.
- Isolated intraventricular hemorrhage warrants additional advanced neuroimaging, including brain MRI with gadolinium, to exclude a choroid plexus tumor or another underlying structural mass lesion. If the MRI is unrevealing, digital subtraction angiography is needed to exclude an intraventricular vascular lesion such as a choroidal artery aneurysm or arteriovenous malformation.
- Asymmetry in venous sinuses is common, and identification of asymmetry between one transverse sinus and its contralateral sinus may be quite normal for a given individual and not signify disease.
- With improving care provided by stroke, neuroendovascular, and neurocritical care teams, the risk of symptomatic hemorrhagic transformation of an ischemic stroke is declining and currently stands at approximately 1% to 3%.
- Intracerebral hemorrhage secondary to septic emboli is overall an uncommon condition and is most frequently seen in immunocompromised individuals, patients with prosthetic heart valves, and IV drug users.
ARTICLE 5: NEUROIMAGING IN ADULTS AND CHILDREN WITH EPILEPSY
Erasmo A. Passaro, MD. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):104–155.
This article discusses the fundamental importance of optimal epilepsy imaging using the International League Against Epilepsy–endorsed Harmonized Neuroimaging of Epilepsy Structural Sequences (HARNESS) protocol and the use of multimodality imaging in the evaluation of patients with drug-resistant epilepsy. It outlines a methodical approach to evaluating these images, particularly in the context of clinical information.
Epilepsy imaging is rapidly evolving, and a high-resolution epilepsy protocol MRI is essential in evaluating newly diagnosed, chronic, and drug-resistant epilepsy. The article reviews the spectrum of relevant MRI findings in epilepsy and their clinical significance. Integrating multimodality imaging is a powerful tool in the presurgical evaluation of epilepsy, particularly in “MRI-negative” cases. For example, correlation of clinical phenomenology, video-EEG with positron emission tomography (PET), ictal subtraction single-photon emission computerized tomography (SPECT), magnetoencephalography (MEG), functional MRI, and advanced neuroimaging such as MRI texture analysis and voxel-based morphometry enhances the identification of subtle cortical lesions such as focal cortical dysplasias to optimize epilepsy localization and selection of optimal surgical candidates.
The neurologist has a unique role in understanding the clinical history and seizure phenomenology, which are the cornerstones of neuroanatomic localization. When integrated with advanced neuroimaging, the clinical context has a profound impact on identifying subtle MRI lesions or finding the “epileptogenic” lesion when multiple lesions are present. Patients with an identified lesion on MRI have a 2.5-fold improved chance of achieving seizure freedom with epilepsy surgery compared with those without a lesion.
This clinical–radiographic integration is essential to accurate classification, localization, determination of long-term prognosis for seizure control, and identification of candidates for epilepsy surgery to reduce seizure burden or attain seizure freedom.
- MRI is essential to classify epilepsy as focal or generalized and guides treatment decisions.
- Clinical anatomic correlation of epileptic auras and seizure phenomenology can increase the yield of identifying a structural abnormality on MRI, particularly when the finding is subtle.
- In patients with new-onset seizures, epilepsy protocol MRI identifies a cause in 53% of cases.
- In patients with chronic focal epilepsy who had a standard MRI, an abnormality was found in 49%. In those who had an epilepsy protocol MRI, an abnormality was found in 72%.
- An epilepsy protocol MRI and an interpretation by an expert neuroradiologist increased the yield of identifying a lesion from 39% to a striking 85% in patients with drug-resistant epilepsy.
- By using an 8-channel phased-array head coil at 3T, 48% more lesions were identified than with a routine 1.5T MRI. In patients with prior epilepsy protocol, 1.5T MRI was interpreted as normal, and 3T phased-array MRI resulted in the detection of a new lesion in 65% of patients.
- The International League Against Epilepsy Neuroimaging Task Force 2019 guidelines for optimal imaging should be followed for all patients with epilepsy using a Harmonized Neuroimaging of Epilepsy Structural Sequences (HARNESS) 3T MRI protocol.
- Many MRI findings are subtle, and the clinician must correlate their relevance to clinical history and clinical neurophysiology.
- In a patient with a single unprovoked seizure, an abnormal MRI showing pathology that causes epilepsy increases the risk for a recurrent seizure twofold and, according to the International League Against Epilepsy, the patient would be classified as having epilepsy even with a normal EEG and would warrant treatment with an antiseizure medication.
- In patients with chronic epilepsy who are seizure-free for 2 or more years, prolonged remission of epilepsy off antiseizure medication is approximately 65%. However, when an etiology is known, the chance for remission is less than 50%.
- MRI can show certain pathologic substrates that predict a poor prognosis for long-term seizure control, such as hippocampal sclerosis, malformations of cortical development, and cavernous malformations.
- In one study, greater than 10% of patients died within 2 years of developing medically intractable epilepsy. Fewer than 2% of patients who may have benefited from epilepsy surgery received it.
- Patients with long-term-epilepsy–associated neuroepithelial tumors, vascular malformation, or hippocampal sclerosis attained seizure freedom rates 2 years after surgery ranging from 71% to 77%.
- Finding a lesion on MRI improves surgical seizure-free success 2.5-fold.
- Children younger than the age of 2 years require a different MRI protocol because of the dynamic changes in myelination during this period. From infancy to 18 months, fluid-attenuated inversion recovery (FLAIR) MRI is less informative since the gray and white matter blend in because of reduced myelination and water content.
- Hippocampal sclerosis is characterized by neuronal loss and gliosis and is seen in 36.4% of all epilepsy surgical specimens, 44.5% of those from adults and 15.0% from children.
- High-resolution MRI is 80% to 90% sensitive for identifying hippocampal sclerosis by visual analysis.
- Although most patients with temporal lobe epilepsy show marked hippocampal sclerosis on pathologic examination, 40% demonstrate no significant cell loss and gliotic changes only.
- The frequency of temporal polar cortex abnormalities was found to range from 28% to 66% in patients with drug-resistant temporal lobe epilepsy, usually ipsilateral to the side of hippocampal sclerosis.
- The amygdala can be abnormally enlarged in patients with epilepsy, indicating amygdalar dysplasia, hamartoma, gliosis, or a low-grade neoplasm or developmental tumor. In amygdalar enlargement, pathology findings include dysplasia with hypertrophic, clustered neurons or astrocytic gliosis.
- Malformations of cortical development are classified into three groups based on the main developmental stage affected, with consideration that alteration of early developmental events often affects later events.
- Malformations of cortical development account for the most common surgical pathologies in children and the third most common in adults undergoing epilepsy surgery, with focal cortical dysplasia representing almost 75% of all malformation of cortical development cases.
- Focal cortical dysplasia type II has been described as a “bottom-of-sulcus dysplasia” resulting from dysplastic features maximal at the sulcal depth, tapering to a relatively normal gyral crown.
- A cleft dimple complex can be a clue to identifying a focal cortical dysplasia. It is defined as the cortex buckling inward, away from the brain surface, with a prominent space between the cortex and leptomeninges (cleft and dimple).
- Focal cortical dysplasia type IIa and type IIb are associated with germline mutations in the mammalian target of rapamycin (mTOR) pathway. These mutations include but are not limited to DEPDC5, NPRL2, and NPRL3 mutations and, in some cases, can be associated with multiple cortical dysplasias, some of which are MRI occult.
- Grey matter nodular heterotopia refers to a collection of neurons in an abnormal location such as the subcortical white matter and subependymal region or under normal-appearing cortex in a laminar pattern. On MRI, the lesions are gray matter isointense on both T1- and T2-weighted sequences.
- Polymicrogyria consists of an excessive number of small gyri with shallow sulci. Polymicrogyria can be (1) focal and limited; (2) focal, unilateral, and extensive; (3) bilateral and symmetric; (4) bilateral and asymmetric; (5) multifocal; or (6) diffuse. MRI shows numerous small gyri with shallow sulci, and the cortical-subcortical junction is often irregular.
- In patients with intractable epilepsy treated with epilepsy surgery, neoplasms account for approximately 22% of cases, with long-term-epilepsy–associated tumors accounting for the majority and ganglioglioma the most common.
- Long-term-epilepsy–associated tumors most commonly occur in the temporal lobe with a mean age of 16 years at seizure onset. They can be associated with focal cortical dysplasia type 1 with cortical disorganization in 80% of patients with long-term-epilepsy–associated tumors and type II cortical dysplasia in 11%.
- Hypothalamic hamartomas are rare, occurring in 1 in 200,000 children. They are typically located between the infundibular stalk anteriorly and the mamillary bodies posteriorly. They are T1 hypointense and T2 hyperintense on MRI. In one-third of cases, they present with gelastic seizures.
- Temporal lobe encephaloceles are herniations of the temporal lobe and meninges through the dura and the skull; they account for 0.30% of patients with newly diagnosed epilepsy and 2.0% to 5.5% of patients with drug-resistant epilepsy.
- Cavernous malformations are composed of well-circumscribed vascular spaces with blood in varying stages of evolution.
- Susceptibility-weighted imaging (SWI) capitalizes on the paramagnetic properties of deoxygenated blood. SWI helps detect microhemorrhages from remote trauma or cavernous malformations and identifies calcification.
- Coregistering positron emission tomography (PET) to three-dimensional epilepsy protocol MRI optimizes the identification of subtle focal cortical dysplasias or helps localize the epileptogenic region.
- Subtraction ictal single-photon emission computerized tomography (SPECT) coregistered to MRI (SISCOM) is a technique in which the interictal SPECT is subtracted from the ictal SPECT and then coregistered to MRI, which enhances the sensitivity, specificity, and interreader reliability of localizing epileptogenic regions and lesions.
- SPECT can show larger regions of cerebral hyperperfusion than the actual epileptogenic region, reflecting regions of seizure propagation rather than onset.
- Functional MRI (fMRI) acquisitions use the blood oxygen level-dependent (BOLD) effect to indirectly infer brain activity through task-related increases in cerebral blood flow via T2* acquisitions.
- Task-based fMRI is widely used in presurgical evaluation to determine language hemispheric dominance, often in planned temporal lobe resection in the dominant hemisphere.
- Magnetoencephalography and magnetic source imaging use direct electrophysiologic measurements of neural activity recording of the magnetic field outside the scalp on a millisecond basis. It is highly accurate in the localization of interictal epileptiform discharges and is more sensitive to tangential dipoles than radial dipoles recorded by scalp EEG.
- Patients with a single tight cluster of dipoles have improved localization compared with patients with scattered dipoles. The MEG coregistered to a three-dimensional epilepsy protocol MRI shows the relationship of the spike dipoles to the cortical anatomy.
- Magnetoencephalography can direct the clinician to identify subtle cortical dysplasia or guide intracranial electrode placement to optimize surgical localization, particularly in MRI-negative patients.
- Multimodality imaging is most useful in MRI-negative epilepsies, where the surgical seizure-free outcome can be 20% or less. It can optimize localization in conjunction with video-EEG and seizure phenomenology, guide intracranial EEG implantation, and, in some cases, identify a previously missed subtle focal cortical dysplasia.
- Fludeoxyglucose positron emission tomography (FDG-PET) shows a functional deficit zone that can be larger than the epileptogenic zone, but in some cases such patterns may have predictive value for a surgical seizure-free outcome.
- Texture analysis using voxel-based modeling of gray-white matter blurring and gray matter intensity from three-dimensional T1-weighted MRI increases the identification of focal cortical dysplasia type II by 40% compared with visual analysis.
ARTICLE 6: IMAGING OF SKULL BASE TUMORS
Wenya Linda Bi, MD, PhD. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):156–170.
This article provides an overview of imaging modalities and findings associated with common skull base tumors including meningiomas and how to use imaging features to guide surveillance and treatment decision making.
Ease of access to cranial imaging has led to a higher number of incidentally diagnosed skull base tumors, which merit careful consideration for management with observation or treatment. The point of origin of the tumor dictates the pattern of anatomic displacement and involvement by the tumor as it grows. Careful study of vascular encroachment on CT angiography, as well as the pattern and extent of bony invasion on CT, abets treatment planning. Quantitative analyses of imaging, such as with radiomics, may further elucidate phenotype-genotype associations in the future.
Combinatorial application of CT and MRI analyses improves the diagnosis of skull base tumors, clarifies their point of origin, and dictates the extent of treatment needed.
- Skull base tumors refer to both tumors whose cell of origin is outside of the brain parenchyma as well as tumors that are physically located in or near the base of the skull.
- Many skull base tumors, such as meningiomas or pituitary microadenomas, are incidentally diagnosed and may be safely observed as the initial strategy.
- The point of origin of skull base tumors dictates their relationship with adjacent nerves, vessels, and the brain because relative anatomic relationships are usually maintained even while absolute anatomic positions are distorted.
- Meningiomas frequently involve the adjacent bone, which should be specifically examined on surveillance imaging.
- Venous sinus occlusion through natural growth of a meningioma leads to rerouting of venous drainage from cortical veins at the anterior and posterior limits of the occluded sinus and does not result in venous infarction on its own.
- Enlarging benign meningiomas typically grow 1 to 2 mm per year; rates faster than this raise concern for more atypical behavior.
- A meningioma growth rate exceeding that of benign meningioma trajectories, irregular tumor shape, intratumoral heterogeneity including the presence of central necrosis or hemorrhage, a knobby or ill-defined pattern of tumor-brain interface, and potentially the extent of peritumoral edema all raise concern for more aggressive behavior.
- Falcine and parasagittal meningiomas are more likely to be higher grade whereas midline anterior skull base meningiomas tend to be benign.
- Solitary fibrous tumors, formerly termed hemangiopericytoma, are a highly vascular mimic of meningiomas and may metastasize outside of the central nervous system.
- Schwannomas demonstrate variable growth rates, with cystic and neurofibromatosis type 2–associated tumors more likely to exhibit faster growth.
- Although contrast-enhanced T1-weighted MRI remains the most common modality to visualize schwannomas, T2-weighted MRI may be suitable for long-term surveillance of schwannoma growth.
- Rathke cleft cysts and neurohypophysial tumors push the pituitary stalk anteriorly, as best appreciated on sagittal imaging, because of their origin posterior to the adenohypophysis.
- Craniopharyngiomas in children are almost exclusively adamantinomatous whereas papillary craniopharyngiomas are found in adults, commonly with a BRAFV600E mutation.
- Chondrosarcomas exhibit pronounced calcification in comparison to chordomas and are typically eccentric toward one side as opposed to midline.
- Epidermoid cysts are best characterized by their avid restricted diffusion on diffusion-weighted imaging sequences.
- Radiomic analyses of conventional tumor imaging may augment the prediction of biological signatures in the future.
ARTICLE 7: IMAGING OF BRAIN TUMORS
Justin T. Jordan, MD, MPH, FAAN; Elizabeth R. Gerstner, MD. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):171–193.
This article focuses on neuroimaging as an essential tool for diagnosing brain tumors and monitoring response to treatment.
Neuroimaging is useful at all stages of brain tumor care. Technologic advances have improved the clinical diagnostic capability of neuroimaging as a vital complement to history, examination, and pathologic assessment. Presurgical evaluations are enriched by novel imaging techniques, through improved differential diagnosis and better surgical planning using functional MRI (fMRI) and diffusion tensor imaging. The common clinical challenge of differentiating tumor progression from treatment-related inflammatory change is aided by novel uses of perfusion imaging, susceptibility-weighted imaging (SWI), spectroscopy, and new positron emission tomography (PET) tracers.
Using the most up-to-date imaging techniques will facilitate high-quality clinical practice in the care of patients with brain tumors.
- Approximately 25,000 primary malignant brain tumors are diagnosed each year in the United States.
- Glioblastoma is the most common malignant primary intracranial brain tumor in adults.
- Keeping a broad differential diagnosis is important for mass lesions, including abscesses, strokes, or inflammatory disease.
- Although CT may show acute changes such as stroke or hemorrhage, gadolinium-enhanced MRI is the preferred imaging modality for brain tumors.
- T1-weighted, T2-weighted, and fluid-attenuated inversion recovery (FLAIR) sequences are critical to diagnosing and treating patients with brain tumors.
- Diffusion-weighted imaging may be helpful to detect ischemic strokes, hypercellularity within tumors (especially lymphomas and high-grade gliomas), and perioperative devitalized tissues.
- Susceptibility-weighted imaging is helpful to identify calcifications in low-grade tumors or hemorrhage in typically higher-grade tumors.
- Perfusion imaging may help visualize vascularity and help distinguish between low- and high-grade tumors, as well as between tumor growth and inflammatory changes.
- MR spectroscopy that measures 2-hydroxyglutarate may aid in diagnosing an isocitrate dehydrogenase (IDH)-mutated tumor and may improve monitoring of treatment response.
- Functional MRI is useful for determining the anatomic location of brain activity for various tasks such as speaking or motor function and may help surgical planning.
- Amino acid positron emission tomography (PET) tracers may aid in distinguishing tumor growth from inflammatory changes.
- Pseudoprogression in high-grade gliomas is often associated with increased contrast enhancement and hyperintensity on T2-weighted and FLAIR images and is caused by inflammatory change.
- Distinguishing tumor progression from inflammatory change is a frequent challenge, and a thorough evaluation may incorporate perfusion MRI, amino acid positron emission tomography, or MR spectroscopy.
- Lower-grade tumors may exhibit inflammatory radiation change through slow progression of hyperintensity on FLAIR images.
- Drugs targeting vascular endothelial growth factor (VEGF) such as bevacizumab may reduce enhancement and hyperintensity on FLAIR images temporarily for high-grade gliomas, a phenomenon known as pseudoresponse.
- Based on expert consensus, the Response Assessment in Neuro-Oncology criteria provide a standardized framework for monitoring brain tumor treatment response.
- Despite their nonmalignant behavior, pilocytic astrocytomas present as heterogeneously enhancing nodules with adjacent cystic structures.
- Subependymal giant cell astrocytomas are a classic feature of tuberous sclerosis complex and are generally found near the foramen of Monro.
- IDH-mutated astrocytomas commonly exhibit the T2-FLAIR mismatch sign, in which T2-weighted images show a hyperintense tumor but the tumor is less hyperintense on FLAIR images.
- Oligodendrogliomas commonly present with seizures, extend to the cortex, and may reveal internal calcification.
- Glioblastoma is generally characterized by a supratentorial mass lesion with heterogeneous enhancement and surrounding hyperintensity on T2-weighted and FLAIR images; some intratumoral hemosiderin and satellite lesions may exist.
- H3 K27–altered diffuse midline glioma is an aggressive tumor that may arise from any midline structure such as thalamus, brainstem, or spinal cord.
- Ependymomas may arise in the supratentorial space, infratentorial space, or spinal cord and have varying molecular differentiation.
- Central nervous system lymphomas in immunocompetent patients are homogeneously enhancing, whereas immunosuppressed patients present with rim-enhancing lesions with occasional necrosis or hemorrhage.
- Nearly 80% of central nervous system lymphoma lesions are close to the ventricular ependyma or meningeal surface, and frequent involvement of the basal ganglia, thalamus, or corpus callosum occurs.
- Although hemangioblastomas may be sporadic, evaluation for underlying von Hippel-Lindau syndrome is important.
- Imaging of the entire neuraxis and spinal fluid sampling are necessary for patients with medulloblastoma because of the high rate of disseminated disease.
- Pleomorphic xanthoastrocytoma classically presents as a cystic, cortically located tumor with an enhancing nodule.
- Brain metastases are usually multiple and within the cerebral hemispheres, especially in end-arterial border zone locations and at the junction of cortex and subcortical white matter.
- Very small metastatic tumors may present as foci of restricted diffusion before growing to show definitive enhancing tumors.
- Imaging is an essential tool for diagnosing and monitoring intracranial brain tumors.
ARTICLE 8: IMAGING IN MOVEMENT DISORDERS
Baijayanta Maiti, MD, PhD; Joel S. Perlmutter, MD. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):194–218.
This article reviews commonly used imaging modalities in movement disorders, particularly parkinsonism. The review includes the diagnostic utility, role in differential diagnosis, reflection of pathophysiology, and limitations of neuroimaging in the setting of movement disorders. It also introduces promising new imaging modalities and describes the current status of research.
Iron-sensitive MRI sequences and neuromelanin-sensitive MRI can be used to directly assess the integrity of nigral dopaminergic neurons and thus may reflect disease pathology and progression throughout the full range of severity in Parkinson disease (PD). The striatal uptake of presynaptic radiotracers in their terminal axons as currently assessed using clinically approved positron emission tomography (PET) or single-photon emission computed tomography (SPECT) imaging correlates with nigral pathology and disease severity only in early PD. Cholinergic PET, using radiotracers that target the presynaptic vesicular acetylcholine transporter, constitutes a substantial advance and may provide crucial insights into the pathophysiology of clinical symptoms such as dementia, freezing, and falls.
In the absence of valid, direct, objective biomarkers of intracellular misfolded α-synuclein, PD remains a clinical diagnosis. The clinical utility of PET- or SPECT-based striatal measures is currently limited given their lack of specificity and inability to reflect nigral pathology in moderate to severe PD. These scans may be more sensitive than clinical examination to detect nigrostriatal deficiency that occurs in multiple parkinsonian syndromes and may still be recommended for clinical use in the future to identify prodromal PD if and when disease-modifying treatments become available. Multimodal imaging to evaluate underlying nigral pathology and its functional consequences may hold the key to future advances.
- The pathologic hallmark of Parkinson disease is the intracellular deposition of misfolded α-synuclein; classic motor symptoms of Parkinson disease manifest only after the loss of midbrain nigral dopaminergic neurons crosses a certain threshold.
- The nigrostriatal dopaminergic neurons project to the striatum, and substantial loss of striatal dopamine has already occurred by the time the classic motor symptoms of Parkinson disease manifest.
- A radiotracer specific for α-synuclein may best reflect pathophysiology of motor as well as nonmotor symptoms in Parkinson disease, but such a radiotracer is not yet available.
- The only radiotracer approved clinically for single-photon emission computed tomography (SPECT) imaging targets the presynaptic dopamine transporter and hence measures the integrity of terminal axons of the nigrostriatal dopaminergic neurons.
- Dopamine transporter (DAT)-SPECT scans demonstrate significantly reduced striatal uptake in the putamen more than the caudate nucleus in Parkinson disease compared with healthy controls; this is usually but not always asymmetric, and this asymmetry may become less pronounced as the disease progresses.
- DAT-SPECT may be more sensitive than clinical examination, as significant depletion of terminal axons and striatal dopamine is likely to occur before clinical symptoms of Parkinson disease manifest.
- The diagnostic accuracy of DAT-SPECT scans is not significantly different from the accuracy of a clinical diagnosis of Parkinson disease; individuals with normal DAT-SPECT scans may develop Parkinson disease in the future.
- DAT-SPECT scans have low specificity, and abnormal dopamine transporter uptake may be seen in atypical parkinsonism and other neurodegenerative disorders; thus, DAT-SPECT does not aid in the differential diagnosis of parkinsonism, limiting its clinical utility.
- False-positive abnormal DAT-SPECT scans may result from underlying strokes, technical issues such as head positioning in the scanner, or exposure to stimulants such as cocaine, amphetamine, or methylphenidate.
- Although identification of individuals with prodromal Parkinson disease is valuable from a research perspective, it will be clinically relevant once disease-modifying treatments for Parkinson disease become available.
- Striatal dopamine transporter uptake has a flooring effect and may reflect nigral cell loss and clinical severity of Parkinson disease only early in the disease process.
- Positron emission tomography (PET) measures of dopamine transporter uptake in the midbrain, unlike the striatum, may reflect nigral cell loss and motor manifestations throughout the full range of parkinsonism.
- Pathologic validation of in vivo PET studies is critical for a complete understanding of proteinopathies; increased Pittsburgh Compound B positron emission tomography uptake reflects the accumulation of fibrillary amyloid-β but not necessarily Alzheimer disease pathology in Parkinson disease.
- [18F]-AV-1451, a PET tracer of tau, demonstrates increased uptake in progressive supranuclear palsy, a tauopathy, but the increase in uptake over time noted on longitudinal PET scans does not correlate with interim clinical progression of progressive supranuclear palsy.
- Radiotracer (-)-5-[18F]-fluoroethoxybenzovesamicol enables quantification of presynaptic cholinergic nerve terminals with good regional specificity; patients with Parkinson disease with a history of falls had greater cholinergic deficits in subcortical structures such as the thalamus and caudate nucleus compared with patients without falls.
- Structural MRI does not show a pattern of atrophy in Parkinson disease that is diagnostic at the individual patient level; MRI in Parkinson disease is indicated if alternative etiologies are suspected.
- MRI in multiple system atrophy may demonstrate atrophy in the putamen, pons, cerebellum, and middle cerebellar peduncle, but these findings have low sensitivity, especially early in the disease process, and are not specific.
- MRI in progressive supranuclear palsy may demonstrate atrophy in the midbrain tegmentum and superior cerebellar peduncle, but these findings have low sensitivity and are not specific; the longitudinal rates of atrophy of the midbrain and pons may aid in the differential diagnosis.
- MRI evidence of strokes affecting the substantia nigra or nigrostriatal pathway may suggest a diagnosis of vascular parkinsonism, but the roles of white matter disease and basal ganglia stroke in its etiopathogenesis are less clear.
- Nigrasome-1, the largest group of dopaminergic neurons in the substantia nigra, appears as a hyperintense signal (“swallow tail”) in the dorsolateral substantia nigra on iron-sensitive T2*-weighted and susceptibility-weighted imaging (SWI) sequences on high-field MRI.
- Dorsal nigral hyperintensity on iron-sensitive T2*-weighted and SWI is lost in Parkinson disease; this finding may be sensitive but not specific. It may help diagnose prodromal Parkinson disease but does not help in the differential diagnosis of atypical parkinsonisms.
- Nigral volume assessed using neuromelanin-sensitive MRI correlates with Parkinson disease duration and severity; decline in nigral volume has been shown on longitudinal scans.
ARTICLE 9: NEUROIMAGING IN DEMENTIA
Shannon L. Risacher, PhD; Liana G. Apostolova, MD, MS, FAAN. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):219–254.
Neurodegenerative diseases are significant health concerns with regard to morbidity and social and economic hardship around the world. This review describes the state of the field of neuroimaging measures as biomarkers for detection and diagnosis of both slowly progressing and rapidly progressing neurodegenerative diseases, specifically Alzheimer disease, vascular cognitive impairment, dementia with Lewy bodies or Parkinson disease dementia, frontotemporal lobar degeneration spectrum disorders, and prion-related diseases. It briefly discusses findings in these diseases in studies using MRI and metabolic and molecular-based imaging (eg, positron emission tomography [PET] and single-photon emission computerized tomography [SPECT]).
Neuroimaging studies with MRI and PET have demonstrated differential patterns of brain atrophy and hypometabolism in different neurodegenerative disorders, which can be useful in differential diagnoses. Advanced MRI sequences, such as diffusion-based imaging, and functional MRI (fMRI) provide important information about underlying biological changes in dementia and new directions for development of novel measures for future clinical use. Finally, advancements in molecular imaging allow clinicians and researchers to visualize dementia-related proteinopathies and neurotransmitter levels.
Diagnosis of neurodegenerative diseases is primarily based on symptomatology, although the development of in vivo neuroimaging and fluid biomarkers is changing the scope of clinical diagnosis, as well as the research into these devastating diseases. This article will help inform the reader about the current state of neuroimaging in neurodegenerative diseases, as well as how these tools might be used for differential diagnoses.
- Alzheimer disease (AD) neuroimaging biomarkers become abnormal in a characteristic order where first amyloid deposition is detected on CSF or positron emission tomography (PET), then tau deposition is detected on CSF or PET, followed by changes in atrophy on MRI, and finally cognitive impairment.
- A research framework for diagnosing AD by classifying patients based on their amyloid status (positive versus negative), tau status (positive versus negative), and neurodegeneration (positive versus negative), as well as cognitive status, has been proposed and widely adopted.
- AD exists on a continuum of cognitive impairment, from cognitively normal individuals with AD pathophysiology (ie, preclinical AD), to mild impairment (mild cognitive impairment [MCI]), and ultimately clinical dementia (clinical AD dementia) with pathology defined by the amyloid, tau, neurodegeneration (A/T/N) framework.
- Patients with AD show widespread degeneration on structural MRI both subcortically, including in the hippocampus, amygdala, basal ganglia, and basal forebrain, and cortically, with the greatest changes in the medial and lateral temporal lobes.
- Structural MRI in patients with MCI shows focal atrophy in the medial and lateral temporal lobes, most especially in the entorhinal cortex and hippocampus, which is intermediate between cognitively normal patients and patients with clinical AD dementia, which can predict future progression to dementia.
- Patients with preclinical AD with normal cognition but positive AD biomarkers or at least one apolipoprotein E ε4 allele (APOE ε4) also show subtle changes in MRI measures of brain structure and function.
- Metabolic imaging with fludeoxyglucose (FDG)-PET shows bilateral hypometabolism in patients with clinical AD, as well as intermediate changes in patients with MCI. Patients with preclinical AD may also show altered metabolism, including either increased or decreased metabolism in several brain regions.
- Amyloid and tau PET imaging allow for visualization of AD pathology across clinical stages, with most clinically diagnosed AD dementia cases showing extensive amyloid and tau binding. The majority of patients with MCI show amyloid binding with some tau binding, and patients with preclinical AD show cortical amyloid binding and minimal tau signal.
- One major area of advancement in the field of AD is the development of blood-based tests that detect amyloid and tau in the plasma. These biomarkers provide excellent prediction of clinical status as well as cerebral amyloid and tau deposition, especially with the plasma phosphorylated tau assays.
- Tau deposition in AD typically follows a staging system originally defined in the pathologic literature (ie, Braak staging). The findings to date suggest that tau may spread through connected networks in the brain that can be measured using functional imaging (eg, functional resting-state imaging) or structural diffusion imaging.
- Although most patients with clinical AD present with memory impairment as the primary symptom, heterogeneity of both clinical symptoms and brain atrophy patterns are observed most commonly in patients with early-onset AD (ie, before the age of 65 years).
- Three subtypes of AD include logopenic aphasia, posterior cortical atrophy, and cerebral amyloid angiopathy, which often occur at younger ages and have distinct clinical and neuroimaging signatures on MRI and tau PET but not on amyloid PET (which is broadly positive across all forms).
- Heterogeneity also occurs in late-onset AD, which is linked to different patterns of brain atrophy and FDG hypometabolic patterns. Some of the subtype definitions map to genetic markers (ie, APOE ε4), higher rates of clinical progression, and more severe cognitive impairment.
- Patients with vascular cognitive impairment most commonly show white matter hyperintensities throughout the white matter of the brain, as well as subcortical infarcts, lacunes, prominent perivascular spaces, and cerebral microhemorrhages on MRI. Although these pathologies can be seen in normal aging, the pathology in vascular cognitive impairment or subcortical ischemic vascular dementia is much more severe and widespread.
- FDG-PET imaging has demonstrated that patients with vascular cognitive impairment have multifocal hypometabolism, which often presents in an asymmetric or scattered pattern or both. This hypometabolism can be cortical or subcortical or both and found near arteries or watershed regions of the brain.
- The majority of dementia cases that come to autopsy have more than one pathologic finding, most commonly AD pathology and small vessel disease, especially in older patients. In life, AD often presents as mixed dementia, reflecting the presence of AD pathophysiology and one or more other suspected pathologies.
- Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) are diseases along the same continuum with the distinguishing factor being the sequence of onset of motor versus cognitive symptoms.
- Patients with DLB and PDD show widespread cortical atrophy on structural MRI, particularly in the posterior cortical regions and relative sparing of the medial temporal lobe compared with patients with AD.
- MRI in patients with multiple system atrophy shows atrophy of the cerebellum, pons, thalamus, substantia nigra, and the parietal and occipital lobes. One characteristic (but nonspecific) sign of multiple system atrophy can be found using T2-weighted imaging, which shows a cruciform hyperintensity in the pons known as the hot cross buns sign.
- FDG-PET studies in PDD and DLB show hypometabolism in the cortex, including the primary visual cortex, with relative sparing of the hippocampus, most distinctively showing the cingulate island sign, which is a relative preservation of metabolism in the posterior cingulate relative to the surrounding parietal and occipital lobes.
- Unique to DLB and PDD, PET and single-photon emission computed tomography (SPECT) measures of dopaminergic neurotransmission are excellent biomarkers for differential diagnosis, with tracers targeting the dopamine transporter and dopamine receptors (ie, D2 receptors) showing reduced binding in the striatum and cortex.
- Frontotemporal lobar degeneration (FTLD) disorders can be classified into two forms by symptoms: (1) behavioral variant FTLD, in which patients show behavioral disturbances among other symptoms; and (2) primary progressive aphasias, which feature language impairments of multiple types.
- FTLD syndromes can feature extrapyramidal or motor symptoms with the FTLD and parkinsonism spectrum consisting of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), as well as FTLD with motor neuron disease (or FTLD-amyotrophic lateral sclerosis).
- Patients with behavioral variant FTLD generally show frontal and temporal lobe atrophy, as well as atrophy in the basal ganglia, thalamus, and other deep gray matter structures, but can vary by underlying pathology (ie, tau versus transactive response DNA-binding protein 43 [TDP-43]).
- Patients with semantic dementia show focal MRI atrophy of the anterior and inferior temporal lobe, with an asymmetric (left more than right) pattern in most cases.
- Patients with progressive nonfluent aphasia show asymmetric perisylvian and anterior insular atrophy with the dominant language hemisphere most affected (usually the left hemisphere in right-handed individuals), as well as in the frontal and temporal lobe (eg, Broca area).
- Patients with CBD show asymmetric atrophy of the frontal and parietal lobes without sparing of the primary motor and sensory cortices, as well as the basal ganglia contralateral to the side most affected with rigidity and apraxia.
- Structural MRI studies in patients with PSP show significant midbrain atrophy, particularly in comparison with the neighboring pons, which is more severe than that seen in CBD. This atrophy pattern has been described as the hummingbird sign on sagittal view and the Mickey Mouse sign or morning glory sign on axial view.
- Patients with FTLD-ALS show atrophy in the frontal and temporal lobes, as well as the anterior cingulate, occipital lobe, and precentral gyrus, which is more severe in patients with FTLD-ALS than in patients with ALS and no FTLD symptoms.
- Patients with behavioral variant FTLD show symmetric frontal hypometabolism on FDG-PET, as well as hypometabolism in the anterior cingulate, parietal lobe, and temporal lobe in later stages.
- FDG-PET studies in semantic dementia have identified reduced metabolism in the left anterior temporal lobe but less significant frontal lobe hypometabolism than in other forms of FTLD.
- Patients with progressive nonfluent aphasia show asymmetric (usually left more than right) frontal cortical hypometabolism in the language-dominant hemisphere, including in the Broca area.
- FDG-PET studies in CBD show asymmetric hypometabolism in the posterior frontal lobes, sensorimotor cortex, and subcortical regions.
- FDG-PET studies in PSP show notable hypometabolism of the prefrontal cortex, caudate, pallidum, thalamus, mesencephalon, and subthalamic nucleus.
- Patients with FTLD-ALS show hypometabolism in the frontal lobe, superior temporal lobe, parietal lobe, occipital lobe, and insula, which is more severe in FTLD-ALS than in ALS without FTLD.
- Amyloid PET scans have shown minimal binding in any subtype of FTLD unless comorbid AD pathology exists.
- Tau PET scans have shown less binding in FTLD relative to that seen in AD, potentially because of less sensitivity of the tracers to non-AD tau conformations. However, the tau PET studies generally show higher tau deposition in regions that mirror the location of atrophy across the FTLD spectrum.
- The primary imaging biomarkers for prion disorders are MRI based, the most sensitive type being diffusion-weighted imaging (DWI). All forms of CJD can show restricted diffusion in the basal ganglia, cerebellum, and diffuse regions of the cortex (“ribboning”), most commonly affecting the frontal and parietal lobes.
- Familial prion protein forms, such as Gerstmann-Sträussler-Scheinker disease and familial CJD, show mixed results with structural MRI measures, with some patients showing no atrophy and others with generalized cerebral and cerebellar atrophy. Patients with fatal familial insomnia may show mild cerebral atrophy and often have restricted diffusion in the thalamus.
- FDG-PET studies in all forms of CJD show widespread and often asymmetric hypometabolism in the cortex and cerebellum, with relative sparing of the basal ganglia and thalamus, whereas familial forms of prion protein disease show cerebral, cerebellar, and subcortical hypometabolism.
- Amyloid and tau PET scans generally show minimal binding in prion protein diseases.
- The differential diagnosis of diseases presenting with or without motor symptoms, such as late-onset AD, atypical AD, CJD, and FTLD, can be improved by using structural MRI and PET techniques.
- Patterns of atrophy and hypometabolism often differ between neurodegenerative disorders and can be used to support a clinical diagnosis, whereas amyloid and tau PET, along with dopaminergic PET or SPECT, can provide support for or rule out a probable diagnosis.
ARTICLE 10: IMAGING OF CENTRAL NERVOUS SYSTEM AUTOIMMUNE, PARANEOPLASTIC, AND NEURO-RHEUMATOLOGIC DISORDERS
Lama Abdel Wahed, MD; Tracey A. Cho, MD, FAAN. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):255–291.
This article provides an overview of the imaging modalities used in the evaluation of central nervous system (CNS) autoimmune, paraneoplastic, and neuro-rheumatologic disorders. An approach is outlined for interpreting imaging findings in this context, synthesizing a differential diagnosis based on certain imaging patterns, and choosing further imaging for specific diseases.
The rapid discovery of new neuronal and glial autoantibodies has revolutionized the autoimmune neurology field and has elucidated imaging patterns characteristic of certain antibody-associated diseases. Many CNS inflammatory diseases, however, lack a definitive biomarker. Clinicians should recognize neuroimaging patterns suggestive of inflammatory disorders, as well as the limitations of imaging. CT, MRI, and positron emission tomography (PET) modalities all play a role in diagnosing autoimmune, paraneoplastic, and neuro-rheumatologic disorders. Additional imaging modalities such as conventional angiography and ultrasonography can be helpful for further evaluation in select situations.
Knowledge of imaging modalities, both structural and functional, is critical in identifying CNS inflammatory diseases quickly and can help avoid invasive testing such as brain biopsy in certain clinical scenarios. Recognizing imaging patterns suggestive of CNS inflammatory diseases can also facilitate the early initiation of appropriate treatments to diminish morbidity and future disability.
- Neuroimaging, especially MRI, can help identify the central nervous system (CNS) compartments predominantly involved in suspected autoimmune or inflammatory disease: parenchymal, meningeal, ventricular, or vascular.
- CT angiography provides good anatomic resolution of large and some medium-size vessels but has poor resolution for smaller vessels.
- Leptomeningitis typically manifests as gyriform or serpentine enhancement following the sulci.
- When assessing extra-axial postcontrast T1-hyperintense lesions, it is important to review in the context of other sequences including T1 precontrast, fluid-attenuated inversion recovery (FLAIR), and susceptibility-weighted imaging (SWI).
- Trauma or neurosurgery may lead to meningeal enhancement in the short term.
- Neurosarcoidosis should be suspected in patients with subacute onset of multiple cranial neuropathies with basal meningitis on MRI.
- Meningioma is often associated with intralesional calcifications and surrounding hyperostosis or bony destruction, which helps distinguish it from focal pachymeningitis.
- Cranial neuropathies, both clinical and radiographic, are a common feature of skull base meningitis.
- IgG4-related disease (as well as neurosarcoidosis) can cause hypophysitis and cavernous sinus disease.
- Direct extension of granulomatous inflammation from sinus to dura is a clue to antineutrophil cytoplasmic antibody–associated vasculitis.
- CNS-limited antineutrophil cytoplasmic antibody–associated vasculitis is typically associated with a hypertrophic meningitis in older women with positive myeloperoxidase antibody.
- Brain MRI in NMDA receptor encephalitis is normal in most patients.
- Compared with autoimmune encephalitis, herpes simplex virus encephalitis is more likely to be unilateral or asymmetric and to have accompanying diffusion-weighted imaging restriction and enhancement.
- Lack of prodromal symptoms, rapid clinical improvement with antiseizure medications alone, and noninflammatory CSF are all clues to distinguish peri-ictal MRI changes from limbic autoimmune encephalitis.
- About 50% of patients with Hashimoto encephalopathy have a normal brain MRI.
- Fludeoxyglucose positron emission tomography (FDG-PET) of the brain can be a more sensitive biomarker than brain MRI for detecting focal or multifocal brain abnormalities in autoimmune encephalitis.
- A gradient of anterior hypermetabolism to posterior cortical hypometabolism, especially in the medial and lateral occipital lobes, has been described in NMDA receptor encephalitis.
- Hypometabolic PET patterns are not specific to autoimmune encephalitis and are seen commonly in the postictal state and in older patients with neurodegenerative disease.
- Once viral causes are ruled out, the presence of bilateral temporal lobe FLAIR hyperintensities is sufficient to diagnose definite limbic autoimmune encephalitis even in the absence of neuronal antibodies.
- Multiple and confluent cortical and subcortical FLAIR hyperintensities are a hallmark of encephalitis with autoantibodies to γ-aminobutyric acid type A (GABAA) receptor.
- Striatal encephalitis with anti-collapsin response mediator protein 5 (CRMP5 or CV2) antibodies may be associated with extensive T2-hyperintense symmetric signal affecting the bilateral caudate and putamen.
- Paraneoplastic diencephalic encephalitis associated with Ma2 antibodies may cause T2 hyperintensities in the medial thalami and midbrain.
- Glial fibrillary acidic protein (GFAP) astrocytopathy is associated with a hallmark MRI finding of periventricular linear radial enhancement on postcontrast T1-weighted sequences.
- For posterior fossa structures, subtle T2 hyperintensity may be more easily appreciated on conventional T2-weighted MRI than on FLAIR sequences.
- Rim-enhancing lesions with central restricted diffusion suggestive of abscess are clues to Listeria infection as the cause of brainstem encephalitis.
- Neuro-Behçet syndrome may be associated with T2 hyperintensity in the ventral pons and midbrain, sparing the red nucleus.
- MRI is often normal early in the course of paraneoplastic cerebellar degeneration although mild T2 hyperintensities may be seen in the cerebellar hemispheres.
- The most commonly associated autoantibodies with autoimmune cerebellar ataxia are anti–glutamic acid decarboxylase 65 (GAD65), anti–contactin-associated proteinlike 2 (CASPR2), and anti–metabotropic glutamate receptor (mGLuR1).
- Approximately 50% of patients with neuropsychiatric lupus have abnormal brain MRI, most commonly manifesting as nonspecific white matter periventricular and subcortical T2 hyperintensities.
- Neuromyelitis optica spectrum disorder (NMOSD) may occur in association with Sjögren syndrome, and patients with optic neuritis or transverse myelitis should be tested for serum aquaporin-4 IgG and myelin oligodendrocyte glycoprotein IgG.
- Brain MRI is abnormal in 95% to 100% of patients with CNS vasculitis.
- Digital subtraction angiography is the most sensitive modality for vascular luminal changes in CNS vasculitis, including alternating areas of stenosis and dilation in at least two separate vascular distributions.
- High-resolution MRI with vessel wall imaging may be helpful in demonstrating enhancement of the vessel walls in vasculitis, but the modality has limited specificity.
- Findings of callosal T2 hyperintensities or “snowball-like” lesions in the corpus callosum in the context of encephalopathy, branch retinal artery occlusion, and hearing loss are highly suggestive of Susac syndrome.
- Confluent and asymmetric T2 hyperintensities in cortical and subcortical areas, in association with microhemorrhage on SWI, are characteristic of cerebral amyloid angiopathy-related inflammation.
- MRI is helpful in determining the length of the lesion (short versus longitudinally extensive transverse myelitis), width (partial versus transverse), and location (eccentric, central, hemicord, anterior versus posterior, conus, tracts, or meningeal).
- The trident sign, which has been described in relation to neurosarcoidosis, demonstrates leptomeningeal or dorsal subpial enhancement that may or may not involve the central canal.
- Involvement of the conus medullaris is a clue to myelin oligodendrocyte glycoprotein-associated disorder as the cause of longitudinally extensive transverse myelitis.
- CT of the chest, abdomen, and pelvis with iodine contrast is a generally accepted first method of screening for occult malignancy or systemic inflammation (eg, sarcoidosis).
ARTICLE 11: IMAGING OF CENTRAL NERVOUS SYSTEM DEMYELINATING DISORDERS
Jan-Mendelt Tillema, MD. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):292–323.
This article summarizes neuroimaging findings in demyelinating disease, the most common being multiple sclerosis. Revisions to criteria and treatment options have been ongoing, and MRI plays a pivotal role in diagnosis and disease monitoring. The common antibody-mediated demyelinating disorders with their respective classic imaging features are reviewed, as well as the differential diagnostic considerations on imaging.
The clinical criteria of demyelinating disease rely heavily on imaging with MRI. With novel antibody detection, the range of clinical demyelinating syndromes has expanded, most recently with myelin oligodendrocyte glycoprotein–IgG antibodies. Imaging has improved our understanding of the pathophysiology of multiple sclerosis and disease progression, and further research is underway. The importance of increased detection of pathology outside of the classic lesions will have an important role as therapeutic options are expanding.
MRI has a crucial role in the diagnostic criteria and differentiation among common demyelinating disorders and syndromes. This article reviews the typical imaging features and clinical scenarios that assist in accurate diagnosis, differentiation between demyelinating diseases and other white matter diseases, the importance of standardized MRI protocols in clinical practice, and novel imaging techniques.
- MRI plays a pivotal role in the diagnostic criteria for central nervous system (CNS) demyelinating disorders.
- In patients with multiple sclerosis (MS), normal-appearing white matter and gray matter are now well known to harbor both demyelinating and neurodegenerative pathology.
- Earlier diagnosis and treatment monitoring for MS rely greatly on MRI. Despite these advances, the diagnosis and distinction between MS phenotypes remain a clinical assessment.
- In MS, radiologic activity can exist without any clinical activity. One of the diagnoses that has gained traction with this pattern is radiologically isolated syndrome, in which MRI lesions are present in asymptomatic patients.
- The risk of conversion to clinically definite MS, whether to relasping-remitting MS or primary progressive MS, is increased with the following risk factors: onset age younger than 37 years, presence of gadolinium enhancement on index scan, or the presence of spinal cord lesions on MRI.
- Patients with progressive MS can still have subsequent disease activity in the form of relapses or new MRI activity, although these are much less common.
- Classic MS lesions are round or ovoid and well circumscribed in the chronic stage.
- With recent advances in three-dimensional fluid-attenuated inversion recovery (FLAIR) imaging, when quality is sufficient, this sequence is actually as sensitive or better than axial two-dimensional T2-weighted images.
- High-quality three-dimensional FLAIR at 3T, more so than double inversion recovery and phase-sensitive inversion recovery, has the best ability to detect cortical MS lesions.
- Open-ring enhancement is highly specific to MS with a pattern in which the opening is facing the gray matter.
- In patients with isolated optic neuritis, the conversion risk to MS is about 25% over 15 years in the absence of brain lesions.
- Optic nerve lesions can have an extensive course throughout the optic nerve, particularly in antibody-mediated optic neuritis (myelin oligodendrocyte glycoprotein and neuromyelitis optica).
- Optical coherence tomography is highly sensitive in the detection of possible previous optic nerve lesions or attacks.
- MRI features in other (antibody-mediated) demyelinating disorders can have distinct characteristics that help distinguish these disorders from MS.
- Acute disseminated encephalomyelitis (ADEM) and optic neuritis are the most common presenting phenotypes of myelin oligodendrocyte glycoprotein–associated disorder.
- Myelin oligodendrocyte glycoprotein–associated disorder lesions can differ from those in neuromyelitis optica and predominantly affect the central gray matter, which is best noted on axial imaging.
- MRI surveillance is typically not felt to be helpful in antibody-mediated demyelinating disease and should be reserved for when new symptoms suggestive of attacks present unless the diagnosis is uncertain.
- Novel MRI acquisition and processing techniques have distinguished some lesion signatures with potential prognostic properties, some of which are slowly finding their way into clinical practice.
- Newer MRI techniques better capture disease that can be visualized beyond the white matter lesions noted on conventional MRI. Lesions can be found in the cerebral cortex with specific acquisitions.
- Quantitative measures of advanced MRI techniques (eg, diffusion tensor imaging) and MR spectroscopy have identified what is known in pathology as normal-appearing white matter involvement.
- Atrophy has been reported throughout the central nervous system in MS, affecting whole brain volume and, in particular, the thalamus.
- Spinal cord lesions can be present without clinical symptoms in MS, and the most common location of spinal cord lesions is within the cervical spinal cord.
- The differential diagnosis should remain broad when the presentation is atypical or in the setting of imaging red flags.
- Harmonization of MRI protocols with the minimal required sequences is highlighted in consensus statements from MS experts, incorporating both diagnostic and disease monitoring purposes in MS.
ARTICLE 12: DIAGNOSTIC ULTRASONOGRAPHY IN NEUROLOGY
Elsa Azevedo, MD, PhD. Continuum (Minneap Minn). February 2023; 29 (1 Neuroimaging):324–363.
Ultrasonography allows neurologists to complement clinical information with additional useful, easily acquired, real-time data. This article highlights its clinical applications in neurology.
Diagnostic ultrasonography is expanding its applications with smaller and better devices. Most indications in neurology relate to cerebrovascular evaluations. Ultrasonography contributes to the etiologic evaluation and is helpful for hemodynamic diagnosis of brain or eye ischemia. It can accurately characterize cervical vascular atherosclerosis, dissection, vasculitis, or other rarer disorders. Ultrasonography can aid in the diagnosis of intracranial large vessel stenosis or occlusion and evaluation of collateral pathways and indirect hemodynamic signs of more proximal and distal pathology. Transcranial Doppler (TCD) is the most sensitive method for detecting paradoxical emboli from a systemic right-left shunt such as a patent foramen ovale. TCD is mandatory for sickle cell disease surveillance, guiding the timing for preventive transfusion. In subarachnoid hemorrhage, TCD is useful in monitoring vasospasm and adapting treatment. Some arteriovenous shunts can be detected by ultrasonography. Cerebral vasoregulation studies are another developing field of interest. TCD enables monitoring of hemodynamic changes related to intracranial hypertension and can diagnose cerebral circulatory arrest. Optic nerve sheath measurement and brain midline deviation are ultrasonography-detectable signs of intracranial hypertension. Most importantly, ultrasonography allows for easily repeated monitoring of evolving clinical conditions or during and after interventions.
Diagnostic ultrasonography is an invaluable tool in neurology, used as an extension of the clinical examination. It helps diagnose and monitor many conditions, allowing for more data-driven and rapid treatment interventions.
- Neurosonology can be used as an extension of the clinical neurologic examination.
- Advantages of neurosonology are that it can be performed at the bedside, is noninvasive, provides real-time accurate information, and allows continuous monitoring.
- An ultrasound machine that provides B-mode echography, color imaging of the vessels, and blood flow velocities spectrum allows extracranial and many intracranial applications, including vascular and parenchymal studies.
- A transcranial Doppler device providing only Doppler spectral analysis is a smaller device that allows hands-free and bilateral monitoring of cerebral hemodynamics with a headframe.
- Atherosclerosis, sickle cell disease, brain and eye ischemia, subarachnoid hemorrhage, suspicion of temporal arteritis or dural fistulas, intracranial hypertension, and cerebral circulatory arrest are some of the settings for neurovascular ultrasonography.
- A comprehensive cerebrovascular ultrasonographic evaluation should include cervical as well as intracranial vessels.
- The degree of stenosis of a cervical internal carotid atherosclerotic plaque can be measured by direct morphologic and velocimetric parameters, as well as by indirect criteria.
- Compensatory intracranial collateral circuits (ophthalmic, anterior communicating, and posterior communicating arteries) provide indirect signs of the hemodynamic effect of a cervical carotid stenosis.
- Higher degrees of stenosis are related to both the decrease in distal perfusion pressure and atheroembolism. Atheroembolic risk is further linked to unstable plaque features.
- Cervical vertebral artery stenosis can be assessed by the decrease in lumen diameter and measurement of blood flow velocity at the stenotic segment and more distally.
- Subclavian steal effect consists of inverted flow from the ipsilateral vertebral artery when a tight stenosis or occlusion of the proximal subclavian artery is present.
- Ultrasound signs of dissection may include an enlarged artery with an eccentric hypoechogenic luminal stenosis, tapering stenosis ending in a string sign, floating intimal flap, and double lumen appearance, with to-and-fro aspect in color and spectral Doppler in the false lumen.
- Concentric hypoechogenic vessel wall thickening is the sonographic hallmark of vasculitis.
- Giant cell arteritis is the most common form of large and medium vessel vasculitis affecting adults, characterized by a hypoechogenic noncompressible thickening of the wall (the halo sign) in the temporal branch of the external carotid artery.
- Transient perivascular inflammation of the carotid artery syndrome associates carotid pain with an eccentric carotid stenosis, disappearing within a few weeks spontaneously or after treatment with anti-inflammatory drugs.
- Isolated hypoechogenic mural thrombi might appear associated with thrombophilia and disappear by lysis, spontaneously, or after anticoagulation therapy.
- Fibromuscular dysplasia is suspected by a string-of-beads appearance in the distal cervical internal carotid artery and the vertebral arteries.
- Carotid webs are potentially thrombogenic and may be implicated in ischemic stroke. Sonographically it appears as a shelf-like membrane in the posterior aspect of the internal carotid artery bulb into the lumen, just beyond the carotid bifurcation.
- When the external carotid artery shows high velocity and low resistance, an arteriovenous shunt may be suspected, especially in a patient with pulsatile tinnitus.
- The thrombolysis in brain ischemia score helps in evaluation of the flow conditions in the symptomatic intracranial artery in acute ischemic stroke, namely before and after recanalization treatment.
- Systolic and mean blood flow velocity cut-offs help diagnose intracranial stenosis and stratify it as <50%, >50%, and >70%.
- Transcranial Doppler (TCD) and transcranial color sonography can accurately detect significant intracranial artery stenosis and occlusion.
- Atherosclerotic stenosis has a more focal and stable blood flow velocity increase than dynamic intracranial stenoses such as those caused by an embolus, dissection, vasospasm, or vasculitis.
- In children with sickle cell disease, screening with TCD for high blood flow velocity (≥200 cm/s) and treatment with regular blood transfusion may result in a 10-fold decrease in the prevalence of strokes.
- Annual TCD screening should be offered for children aged 2 to 16 years with sickle cell disease of the types HbSS or Sβ0 thalassemia.
- In patients with subarachnoid hemorrhage, vasospasm can be monitored with TCD, which helps adjust medical and intervention therapy aiming to prevent delayed cerebral ischemia and cerebral infarction.
- TCD can diagnose vasoconstriction related to reversible cerebral vasoconstriction syndrome in the proximal cerebral arteries, although there are no standardized blood flow velocity criteria.
- Changes in blood flow velocity over time in patients with reversible cerebral vasoconstriction syndrome may be more informative than the isolated values.
- TCD can be used to monitor cerebral hemodynamics during acute stroke and in the neurocritical setting, as well as before, during, and after therapeutic interventions.
- TCD and transcranial color sonography allow for monitoring intracranial pressure changes. With intracranial pressure increase, cerebral blood flow velocity, mainly diastolic, decreases.
- Cerebral circulatory arrest is indicated by no diastolic flow for at least 30 minutes in the middle cerebral arteries and the basilar artery, and decreased systolic blood flow velocity.
- TCD and transcranial color sonography are highly accurate ancillary tests for cerebral circulatory arrest confirmation.
- TCD and a nontranspulmonary gaseous contrast injection are a reliable and less invasive complement to gold standard transesophageal echocardiography in the diagnosis of a patent foramen ovale and enable the detection of extracardiac right-to-left shunt.
- The size of a patent foramen ovale measured by transesophageal echocardiography correlates with the amount of microembolic signals observed by TCD.
- Microembolic signal monitoring is useful in evaluating arterial lesion stroke risk and as a surrogate marker of antithrombotic drug efficacy.
- Microembolic signal monitoring is performed over 30 to 60 minutes, usually with bilateral 2-MHz probes fixed in a headframe.
- Reduced cerebral autoregulation is associated with worse outcome in acute stroke and in the neurocritical care setting.
- Functional TCD studies may allow identification of the dominant hemisphere and identification of early neurovascular unit dysfunction in cerebrovascular pathologies.
- Raised flow velocities in collateral venous drainage are the most frequent finding in patients with cerebral venous sinus thrombosis, although it has low sensitivity.
- Ultrasound evaluation of the optic nerve allows for detection of signs of increased intracranial pressure, namely increased optic nerve sheath diameter and raised papilla.
- Especially in the neurocritical care setting, ultrasonography can be useful for the measurement of pupil reactivity.
- Analysis of orbital vascularization may provide evidence of central retina artery occlusion, which has a worse prognosis if an embolic echogenic spot sign is present.