Imaging Considerations and Thoracic Diseases in Females

Abstract

Females have unique physiological considerations that must be considered during image acquisition and interpretation. Familiarity with imaging of pregnant and lactating patients requires modifications from standard protocols to mitigate radiation-induced risk to both the mother and the fetus. Manifestations in the chest related to conception, pregnancy, and gynecologic pathologies are female-specific. Furthermore, there are a number of conditions that exclusively or disproportionately affect females, including diffuse lung diseases. Here, we review the expected normal findings and variant appearances of diseases in female patients on chest imaging to help the radiologist arrive at the correct diagnosis and avoid diagnostic pitfalls. In addition, the general principles of thoracic imaging in women of reproductive age are discussed.

Although many disease processes and their imaging manifestations are quite similar between males and females, there are many instances when sex-specific considerations are necessary. Before image acquisition, pregnancy and lactation status should be ascertained to decide on the most appropriate imaging modality and use of intravenous contrast. Fetal developmental stage, pregnancy, and lactation status also need to be accounted for when prescribing imaging parameters and radiation dose reduction techniques. Familiarity with normal sex-based variations in anatomy and diseases prevalent or exclusively present in females is essential to accurately interpret imaging studies.

PERINATAL AND UNIQUE IMAGING CONSIDERATIONS IN FEMALES

Choice of Imaging Modality, Radiation Dose Consideration, and Contrast Agent Use

The potential of teratogenic and carcinogenic effects of ionizing radiation and adverse effects of intravenous (IV) contrast media require special consideration when imaging females in the perinatal period. The appropriateness of an imaging test, protocol modifications, and use of contrast material are essential. When feasible, ultrasound should be used as a first-line imaging investigation due to the absence of risks associated with ionizing radiation to both the mother and the fetus.^1,2 If applicable, chest radiography (CXR) should be the modality of choice in the thoracic evaluation of acute conditions in pregnancy, with radiation dose to the fetus being negligible with modern technologies.¹ Although thoracic computed tomography (CT) examinations do result in higher levels of radiation exposure compared with CXR, the dose to the fetus remains negligible when the fetus is outside of the scan field. For example, the estimated dose to the fetus for both a routine chest CT and computed tomography angiography (CTA) of the pulmonary arteries (PA CTA) is ~0.2 mGy, whereas the dose from a coronary CTA is ~0.1 mGy.¹ Tube current modulation, available on most current CT scanners, also helps to reduce the radiation dose during image acquisition.¹ Patient lead shielding is not recommended during the scanning since it can interfere with automatic exposure control and actually increase the fetal radiation dose, and obscure anatomic details.³ Overall, fetal risks from radiation doses of <50 mGy are considered negligible, and doses from thoracic CT are well below this threshold.²

No harm to the fetus from maternal IV iodinated CT contrast use is consistently reported, with most iodinated contrast agents classified as a category B by the FDA. As a result, the ACR does “not recommend withholding the use of iodinated contrast agents in pregnant women of potentially pregnant patients when it is needed for diagnostic purposes.⁴”

Pulmonary embolism (PE) and deep venous thrombosis (DVT) have special consideration in pregnancy. The risk of DVT in pregnancy is 5 times greater when compared with nonpregnant patients of the same age group.⁵ Lower extremity venous ultrasound (vUS) and CXR are considered the first-line tests, given their lowest radiation dose profile to the fetus. If lower extremity vUS is positive for DVT, no further imaging is required, as anticoagulation is usually warranted in this situation. If vUS is negative, PA CTA or lung scintigraphy (in the setting of a normal chest radiograph) is considered as the next test.² Radiation doses for the perfusion portion of the ventilation/perfusion (V/Q) scan can be reduced in pregnant patients with a reduced dose of the radiotracer and compensatory increase in imaging time, and omission of the ventilation component if the perfusion portion is normal.² Radiation dose to the fetus is higher with V/Q scanning compared with PA CTA during all trimesters⁶; however, the dose to the maternal breast is lower with scintigraphy.⁷ One of the major disadvantages of scintigraphy is the inability to suggest alternative diagnoses in comparison with CTA.² Variations exist in the accuracy and nondiagnostic rates of each modality; however, a meta-analysis suggests that the 2 tests are comparable in terms of nondiagnostic rates and negative predictive value.⁷

Modifications to PA CTA, and other thoracic CT protocols can help to reduce the radiation dose further without compromising the quality of the study. Use of a standard 15-second delay after the start of contrast injection (instead of automatic triggering based on a set threshold and serial monitoring scans) has been shown to reduce dose while maintaining diagnostic image quality.⁸ Concomitant reduction of kVp, mAs, and z-axis coverage will also decrease the radiation dose. Exclusion of the lung apices on PA CTA is suggested, given the relatively low incidence of isolated apical pulmonary emboli and overall lower detection rate by CTA.⁹ Higher concentration and volume of contrast, faster rate of injection, and/or image acquisition during shallow inspiration may help to improve image quality and prevent “transient interruption of contrast,” and compensate for normal physiologic changes seen in pregnancy such as higher heart rate, cardiac output, and plasma volumes that may affect the quality of PA CTA.^10,11

MRA plays a role in imaging females of reproductive age, including pregnancy, given its advantage of no ionizing radiation. However, noncontrast-enhanced MRA is rarely used in clinical practice, due to the wider availability, ease of acquisition and interpretation, and the relatively high negative predictive value and sensitivity of CTA for the detection of pulmonary emboli (median negative predictive value of 100% and median sensitivity of 83% in a Cochrane review of 11 studies¹²). At the same time, noncontrast-enhanced MRA with rapid sequences has demonstrated reasonable sensitivity (88.5%) and specificity (86.6%) for the detection of proximal PE in a small study.¹³ Slow infusion of IV ferumoxytol, an iron-based compound with prolonged blood pool time, off-label as a contrast agent, has shown good success in PE evaluation; however, it is considered a category C medication during pregnancy by the FDA.^14,15

Gadolinium-based IV contrast media use during pregnancy has not been well studied in humans and, therefore, the safety has not been well established. However, no adverse mutagenic effects to human fetuses were reported with the doses used for magnetic resonance imaging (MRI) examinations.⁴ On the basis of animal studies, the FDA has classified these agents as category class C. Similarly, the ACR (American College of Radiology) recommends that these agents be administered with caution in pregnancy and only if the potential benefits outweigh the unknown risk to the fetus, with no imaging alternative to answer the clinical question. If use is indicated, the ACR also recommends that informed consent be obtained from the patient.⁴

Imaging During Lactation

The safety of iodinated and gadolinium-based IV contrast agents and radiation dose are important to consider during lactation. Since only a very small amount of both iodinated and gadolinium-based contrast material is excreted in breast milk (<1%) and absorbed by the infant’s gastrointestinal system, the use of both classes of contrast agents with continuation of normal breast feeding is considered safe and recommended.⁴ Ultimately, the decision is left to the mother, with optional pumping and discarding milk from the time of, and up to 12 to 24 hours after, contrast administration.⁴ Before deciding to temporarily discontinue breast feeding after IV contrast administration, the mother should be counseled that even short periods of cessation could lead to weaning.¹⁶

In contrast to CT and MRI studies, the breast-fed infant will be exposed to radiation through radioactivity in the breast milk and by physical proximity to the mother after nuclear medicine examinations. The recommended length of temporary breast-feeding interruption depends on the physical and biologic half-life of an individual radiopharmaceutical; however, the resultant dose to the infant should be less than 1 mSv. After the administration of ⁶⁷Gallium-citrate and ¹³¹I-sodium-iodide, complete cessation of breast feeding is advised.¹⁶

Although it is theorized that during pregnancy and lactation, mammary tissue may be more susceptible to the mutagenic effects of ionizing radiation, a study of both V/Q nuclear scans and thoracic CT examinations during the perinatal period did not show a statistically significant increase in early-onset breast cancer, although the long-term risk is uncertain.¹⁷ As a result, minimizing radiation dose to the breast tissue during this time, when possible, while maintaining diagnostic image quality is prudent.

PREGNANCY-RELATED PATHOLOGIC CONDITIONS

Acute Pulmonary Edema (APE) and Acute Respiratory Distress Syndrome (ARDS)

APE and ARDS result from both obstetric and non–obstetric-related conditions in pregnancy.¹⁸ Predisposing physiological changes leading to APE include increased cardiac output, anemia, and low colloid osmotic pressure.¹⁹ Nonphysiological risk factors include preexisting maternal cardiovascular disease, preeclampsia, and peripartum cardiomyopathy. On CXR, findings in APE are similar to edema in a nonpregnant patient (Fig. 1) and, depending on the severity, include upper lobe vascular redistribution, septal (Kerley B) lines, alveolar opacities, and pleural effusions.²⁰ On CT, interlobular septal thickening, ground glass opacities (GGO), and pleural effusions are seen.

FIGURE 1: Peripartum edema. A 26-year-old-woman presented with dyspnea 5 days postpartum and showed normal cardiac biventricular size and function by echocardiography. Frontal chest radiograph (A) demonstrates bilateral pleural effusions and diffuse bilateral interstitial opacities. Axial images from an PA CTA (B–E) demonstrate bilateral pleural effusions with adjacent left basilar atelectasis. Scattered small faint groundglass opacities and interlobular septal thickening (arrows, C, E) are also present. The findings are consistent with pulmonary edema. It is noteworthy that the study was negative for pulmonary emboli.

ARDS is associated with a maternal mortality rate of nearly 25% and linked to both nonobstetric (sepsis, pneumonitis, blood transfusions, and trauma) and obstetric (amniotic fluid embolism [AFE], preeclampsia, and retained products of conception) causes.^18,21 The imaging appearance of ARDS on CXR and CT is similar to that in nonpregnant individuals and includes bilateral alveolar opacities (usually with extensive air-bronchograms) and pleural effusions.²²

AFE

AFE is a rare but severe potential complication of pregnancy with a high mortality rate (up to 86%).^23,24 The mechanism is linked to the immune and pro-thrombotic cascade that leads to anaphylaxis, septic shock, edema, disseminated intravascular coagulation, and cardiopulmonary collapse. This results from amniotic fluid entering the venous system through small tears in uterine veins after membrane rupture and labor.^23,25,26 Findings on CXR are similar to other causes of noncardiogenic APE (Fig. 2). Microemboli are below the resolution of CT; however, ill-defined centrilobular ground glass nodules may be present. Neither of these findings are specific and may also be encountered in APE and pulmonary hemorrhage, among other entities.^25,26 CT is usually considered to exclude other etiologies such as an acute PE.²⁵

FIGURE 2: Amniotic fluid embolism. A 30-year-old woman presented with postpartum dyspnea. Axial CT images from cranial to caudal (A–D) reveal bilateral consolidative and ground glass airspace opacities, greatest in the bilateral lower lobes. Small bilateral effusions are also present. The findings were considered to be related to amniotic fluid embolism; however, noncardiogenic pulmonary edema and infectious pneumonia can also have this appearance.

Ovarian Hyperstimulation Syndrome (OHSS)

OHSS is the result of iatrogenic changes due to ovarian induction, occurring during the luteal phase of the menstrual cycle or early pregnancy.^27,28 The reported incidence varies depending on the classification scheme, clinical situation, and stimulation protocol used, but can reach up to 33%.^27,28 Imaging manifestations include bilateral ovarian enlargement with multiple ovarian cysts or follicles and ascites (Fig. 3) due to increased vascular permeability. The diagnosis is established by ultrasound, CT, or MRI.²⁷ Findings on CXR include pleural effusions and adjacent compressive atelectasis, with patients presenting with dyspnea and tachypnea.²⁸ Pleural effusions are more common on the right side and may be accompanied by an elevated hemidiaphragm. Approximately 2% of patients with severe OHSS have PE and 2% develop ARDS.^28,29

FIGURE 3: Ovarian hyperstimulation syndrome. A 30-year-old female presented after recent oocyte removal. Axial CT images at the level of the lung bases (A) demonstrate bilateral pleural effusions (arrows). Axial (B) and coronal (C) images of the abdomen reveal extensive abdominopelvic ascites (*) and markedly enlarged bilateral ovaries with increased number of peripherally placed cysts, with some of the cysts of complex attenuation (arrowheads).

Gestational Trophoblastic Neoplasms (GTN)

GTN are a group of malignant neoplasms within the larger category of gestational trophoblastic diseases. GTN include invasive moles, choriocarcinoma, and placental and epithelioid trophoblastic tumors.³⁰ CXR and CT are the primary modalities for the evaluation of thoracic metastases in the setting of GTN, which are associated with an unfavorable prognosis.³¹ Thoracic metastatic disease most commonly presents with multiple well-defined round, solid noncalcified pulmonary nodules (Fig. 4). A halo of ground glass attenuation, due to neoplastic vascularity and tumorous infiltration, may surround the nodule (Fig. 5).³⁰ Cavitation of the nodules may result in pneumothorax in the setting of subpleural location and rupture.³⁰ Pulmonary arterial tumor embolization is less common, although classically presents with irregular beaded appearance of the distal pulmonary artery branches and occasionally results in pulmonary infarction (with classic peripheral wedge-shaped consolidative and/or GGO).³⁰ Calcification of treated pulmonary metastases can occur.³⁰ Pulmonary arteriovenous malformations (AVMs) after chemotherapeutic treatment of metastatic choriocarcinoma should be considered if one or several pulmonary nodules persist after other nodules have resolved posttreatment. As in pulmonary AVMs due to other etiologies, CT may reveal a feeding pulmonary artery and draining pulmonary vein. Larger AVMs are linked to hemoptysis and/or dyspnea, and cerebral complications from paradoxical emboli.³⁰

FIGURE 4: GTN. CXR (A) and axial CT (B) images demonstrating multiple well-circumscribed, rounded pulmonary nodules (arrowheads) in this young woman with a metastatic GTN. Coronal CT image through the abdomen (C) demonstrates a gravid uterus. Case courtesy of Jeffrey Kanne, MD, PhD, University of Wisconsin-Madison.

FIGURE 5: Choriocarcinoma metastasis. A 36-year-old woman presented with hemoptysis, persistent vaginal bleeding, and elevated beta-hCG after a presumed miscarriage. Axial chest CT (A) demonstrates a pulmonary nodule in the lateral right lower lobe with a solid noncalcified central component and a peripheral rim of ground glass attenuation (arrowhead). Wedge resection specimen (B) revealed metastatic choriocarcinoma.

Lymphangioleiomyomatosis (LAM)

LAM is a multisystem neoplastic disorder of smooth muscle cell proliferation with both thoracic and abdominal manifestations. LAM may be sporadic or associated with tuberous sclerosis complex (TSC), with the sporadic form almost exclusively affecting females of reproductive age. In contrast, LAM in males is nearly all associated with TSC.³² The most common presenting symptoms of LAM include dyspnea, pneumothorax, and cough.^32,33 The course and symptoms of LAM in females may be exacerbated during pregnancy and menstruation.³²

On CT, multiple, well-circumscribed, bilateral thin-walled air cysts throughout both lungs, diffusely distributed in axial and craniocaudal directions, are encountered (Figs. 6A, B).^32,34 The size of the cysts correlates with the disease severity.^32,33 Cyst shape is most commonly round.³³ Lung parenchyma between the cysts is usually normal. Occasionally, ground glass may be present due to hemorrhage, edema, or smooth muscle cell proliferation in the alveolar walls.³³ Air trapping within the intervening normal lung parenchyma is uncommon.³³ Additional findings include solid, noncalcified pulmonary nodules, smooth thickening of the bronchovascular bundles and interlobular septa, and mediastinal lymphadenopathy.³⁴ On CXR, lung volumes are preserved or increased, with the appearance of reticular opacities due to summation of cysts. Pleural effusions are not uncommon, reported in approximately one-third of the patients on CXR and up to two-thirds of the patients on CT.^32,33,35 The chylous content of the pleural effusion often has a CT attenuation similar to that of pleural transudate.³² Chylous effusions often recur and pleurodesis may be necessary. However, pleurodesis may lead to the formation of pleural adhesions and chylous fluid buildup elsewhere in the body.^32,33 Mediastinal ganglia and thoracic duct enlargement have also been reported.³³

FIGURE 6: Tuberous sclerosis (TS) and LAM in a 53-year-old woman. Coronal images through the lungs (A, B) demonstrate multiple small, spherical, thin-walled cysts that are relatively uniformly distributed from the apices through the bases with normal intervening lung parenchyma. Multiple tiny 2 to 3 mm solid noncalcified pulmonary nodules were also present, likely representing multifocal micronodular pneumocyte hyperplasia (MMPN, not shown), which is associated with LAM. Coronal images through the lower chest and upper abdomen (C, D) demonstrate small fat-attenuation foci in the right ventricular myocardium (arrowhead, C), which can be seen in the setting of TS and are distinct from rhabdomyomas, also associated with TS. Additional fat-containing lesions are present in the liver (closed arrows, C, D) and bilateral kidneys (open arrows, D), consistent with angiomyolipomas. Several small sclerotic osseous foci were also present (not shown). This constellation of findings is consistent with LAM in the setting of TS.

In the abdomen, manifestations include renal and hepatic angioleiomyomas, usually identifiable by the presence of macroscopic fat (Figs. 6C, D), and retroperitoneal leiomyomas, and chylous ascites.^32–34

The classic clinical triad of TSC is epilepsy, intellectual disability, and cutaneous angiofibromas.³² Imaging findings in TSC also include pulmonary and extrapulmonary manifestations. Extrapulmonary findings are subependymal giant cell tumors of the brain, retinal hamartomas, cardiac rhabdomyomas, myocardial fatty foci (Fig. 6C), and renal cysts.^32,36 In the lungs, in addition to the cysts, scattered small pulmonary nodules may be encountered, reflecting multifocal micronodular pneumocyte hyperplasia.³²

Lung transplantation is reserved for the end-stage disease, with the recurrent disease occurring in rare posttransplantation, with only 10 case reports in the literature in 2017.^32,37 For less severe cases, sirolimus (rapamycin), an FDA-approved mTOR inhibitor, is reported to decrease the level of serum vascular endothelial factor D and rate of lymphangiogenesis, thus stabilizing lung function and improving the quality of life.³⁸

CONNECTIVE TISSUE DISEASES

Systemic Lupus Erythematosus (SLE)

SLE is a systemic autoimmune disorder characterized by the production of antibodies to components of the cell nucleus, which results in inflammation, immune complex deposition, and vasculopathy involving multiple organs.³⁹ In adults, SLE is nine times more common in females than males, typically presenting during the reproductive years.⁴⁰ SLE is associated with antiphospholipid antibody syndrome (APLAS), manifesting with arterial and venous occlusions, thromboses, pregnancy complications (spontaneous abortions and preeclampsia), and thromobocytopenia.^41,42 In the thorax, SLE involves pleura, pericardium, lung parenchyma, respiratory muscles, and the cardiovascular system.

Serositis in SLE is common, affecting both pleura and pericardium. Pleuritis is the most common intrathoracic system finding in SLE, with an incidence of 45% to 83%.^43,44 Pleuritis can be classified as either “dry” or “wet.” “Dry” pleuritis presents with painful respirations and few, if any, imaging findings, whereas the “wet” variant presents with bilateral exudative pleural effusions.⁴⁵ The latter needs to be differentiated from empyema or transudates due to heart failure.⁴⁵ Long-standing inflammation produces pleural thickening and fibrosis involving visceral and parietal pleural layers and may be associated with rounded atelectasis.^41,45 SLE pericarditis (Fig. 7) has an incidence of 40% to 50% and can be adhesive or exudative.^44,46 When present, pericardial effusions are usually small and cardiac tamponade is rare.⁴⁶

FIGURE 7: SLE manifestations in a 22-year-old patient presenting with chest pain. Short-axis triple inversion recovery MRI (A) demonstrates pericardial edema (arrowhead) and a small pleural effusion (arrow). Short-axis late gadolinium enhancement MRI (B) demonstrates circumferential pericardial enhancement (arrowhead) and pleural enhancement (arrow). Findings are consistent with acute lupus pericarditis and pleuritis. Axial T1-weighted double inversion recovery images (C) shows dilated central pulmonary artery (asterisk), consistent with the patient’s known pulmonary hypertension. Axial image from a CTA chest performed the day before assess for pulmonary emboli (D) also shows the bilateral pleural effusions with adjacent compressive atelectasis (arrow). No pulmonary emboli were present.

Other cardiovascular manifestations also include myocarditis, corticosteroid-induced cardiomyopathy, vasculopathy (due to increased incidence of vasculitis and atherosclerosis), and endocarditis.⁴⁴ The latter ranges from thickened valves to a more severe form as Libman-Sacks (sterile) endocarditis, which is linked to complement deposition.⁴⁴ Cardiac MRI is used for functional, morphologic, and tissue evaluation of the heart along and pericardium, with echocardiography often added for valve assessment.⁴⁷

Pulmonary abnormalities in SLE include pneumonia, pulmonary hemorrhage, lupus pneumonitis, and chronic interstitial pneumonitis.⁴¹ Infectious pneumonia is the most common cause of pulmonary opacities in the setting of SLE⁴⁵ due to underlying immune dysregulation and immunosuppressive medications.^41,45 Pulmonary interstitial pneumonitis in SLE is less common than in the other connective tissue diseases, with the most common histopathologic patterns of organizing or nonspecific interstitial pneumonia (NSIP).⁴⁴ On CT, it presents with irregular linear subpleural opacities, interlobular septal thickening, GGO, reticulation, and architectural distortion.⁴² These findings are more common in the setting of SLE associated with APLAS.⁴² Another pulmonary imaging manifestation in SLE is related to complement deposition and small-vessel vasculitis, resulting in diffuse alveolar hemorrhage⁴⁸ that presents with bilateral GGO and consolidative opacities on CT (Fig. 8) and acute chest pain and dyspnea clinically.⁴⁵

FIGURE 8: Diffuse alveolar hemorrhage in the setting of SLE. A 40-year-old woman with a history of SLE presenting with acute chest pain and mild hemoptysis. No infectious symptoms or corresponding lab findings were detected. Axial (A) and coronal (B) CT images on pulmonary windows show bilateral ill-defined patchy ground glass opacities in both lower lobes most consistent with diffuse alveolar hemorrhage. Case courtesy of Jeffrey Kanne, MD, PhD, University of Wisconsin-Madison.

Respiratory muscle dysfunction may lead to elevated hemidiaphragms with adjacent atelectasis on imaging and restrictive changes on pulmonary function tests.⁴¹ The severe manifestation of this finding is referred to as “shrinking lung syndrome.” Shrinking lung syndrome is a rare complication of lupus, with an incidence of 0.5% to 1.1%, with a female to male ratio of 17:1.⁴⁹ Its pathophysiology is largely unclear, with suggested theories ranging from microatelectatic changes due to the lack of a surfactant and increased surface tension, pleural adhesions, and diaphragm dysfunction from phrenic nerve palsy and SLE-induced myopathy.⁵⁰ On imaging, decreased lung volumes, pleural effusions, pleural thickening, atelectasis, and diaphragmatic elevation are present (Fig. 9).⁴⁸

FIGURE 9: Shrinking lung syndrome (SLS) in the setting of SLE in a 44-year-old woman. Sequential chest radiographs demonstrate a normal appearance (A), followed by decreased lung volumes, elevation of both hemidiaphragms, and bibasilar atelectasis on a radiograph performed several years later (B) consistent with SLS. Case courtesy of Jeffrey Kanne, MD, PhD, University of Wisconsin-Madison.

Pulmonary arterial hypertension (PAH) in individuals with SLE occurs with an incidence of 1% to 18%, with 95% of patients being women.⁵¹ Raynaud’s phenomenon, renal involvement, and vasculitis with digital gangrene and skin changes are among the predictive factors of PAH.⁵¹ In addition, associations with APLAS, recurrent thromboemboli, and chronic interstitial lung disease (ILD) are reported.⁴¹ On CT, enlarged central pulmonary arteries with or without pruning of distal branches are observed. Mosaic attenuation of the lung parenchyma and an enlarged and hypertrophied RV may be present in cases of chronic thromboembolic PAH.

Sjogren Syndrome (SS)

SS is an autoimmune disorder related to the production of antibodies against cytoplasmic peptides.⁵² SS is more prevalent in females than males.⁵² Glandular involvement with sicca symptoms, usually involving the eyes and salivary glands, is common.⁵² Thoracic manifestations include airway abnormalities, interstitial pneumonias, and lymphoproliferative disorders. Airways involvement may result in bronchiectasis, bronchial wall thickening, mosaic attenuation of the lung parenchyma, and centrilobular nodules.⁵² These changes are considered to result from destruction of exocrine glands or cell infiltration.⁵² ILD manifestations include NSIP, usual interstitial pneumonia, organizing pneumonia, and lymphocytic interstitial pneumonia.⁵³ The most common radiologic and histologic pattern in SS is NSIP, seen in 45% of the cases.^53,54 Lymphocytic interstitial pneumonia results from diffuse lymphoid hyperplasia and is most often reported in association with SS, affecting twice as many women as men.^55,56 It presents on CT with poorly defined centrilobular nodules, subpleural nodules, bronchovascular thickening, septal thickening, diffuse ground glass attenuation, randomly distributed cysts, and lymph node enlargement^55,56 (Fig. 10). Another systemic disorder, pulmonary amyloidosis, in association with SS is uncommon, with most cases due to nodular AL amyloidosis.⁵⁷ A review of the literature found 37 cases, nearly all of which occurred in women, with the most common CT findings of multiple nodules and cysts. In addition to pulmonary amyloidosis, SS is associated with an 3% to 5% increased risk of non-Hodgkin lymphoma, particularly marginal zone B cell and mucosa-associated lymphoid tissue lymphomas.⁴⁴ On thoracic CT, these most commonly present with new or enlarging nodules or masses, consolidative or mixed opacities, mediastinal lymphadenopathy, and pleural effusions.⁵²

FIGURE 10: Sjogren syndrome and lymphocytic interstitial pneumonia (LIP) in a 58-year-old woman. Axial CT images through the lungs from cranial to caudal (A–D) demonstrate multiple thin-walled cysts that are relatively evenly distributed. Increased background of ground glass attenuation with more discrete scattered small patchy groundglass opacities is present bilaterally. The findings are consistent with LIP.

Systemic Sclerosis

Systemic sclerosis is an autoimmune disease that results in fibrosis of the skin and internal organs and small-vessel vasculopathy. It affects reproductive-age women more often than men.⁵⁸ Pulmonary involvement occurs in >80% of the patients, with ILD being the most common manifestation.^44,59 Other sequelae include PAH, pleural effusions, respiratory muscle weakness, and aspiration due to esophageal dysmotility.⁴⁴

An NSIP pattern of ILD is the most common, followed by usual interstitial pneumonia.⁵⁹ Organizing pneumonia and obliterative bronchiolitis are less common.⁵⁹ NSIP typically manifests on CT as bilateral lower lung predominant confluent GGO in the cellular subtype, with immediate subpleural sparing (Fig. 11). Peripheral reticular opacities, traction bronchiectasis, and honeycomb change are more common in the fibrotic subtype of NSIP.^59,60

FIGURE 11: Systemic sclerosis-related interstitial lung disease in a 60-year-old woman with systemic sclerosis and dyspnea. Axial CT images (A–D) demonstrate lower lung predominant ground glass opacities, intralobular septal thickening, and bronchiectasis. No macroscopic honeycombing is evident. Areas of immediate subpleural sparing are present (arrows, B–D). The findings are consistent with an NSIP pattern of ILD, in the setting of known systemic sclerosis.

NONTUBERCULOUS MYCOBACTERIAL INFECTION

Mycobacterium avium intracellulare complex (MAC) is a chronic nontuberculous mycobacterial pulmonary infection. The nodular bronchiectatic subtype of MAC has a predilection for Caucasian women older than 50 years of age that most commonly presents with chronic cough.^61–63 Subcentimeter pulmonary nodules, cylindrical bronchiectasis, and endobronchial mucous plugging, with predilection for the right middle lobe and lingula, are classic CT findings (Fig. 12).^61–63 Cavitation, GGO, and lymphadenopathy are rarely seen in MAC in immunocompetent patients.^61,62 The extent of the disease on CT has been shown to correlate with the severity of pulmonary functional impairment.⁶⁴

FIGURE 12: Mycobacterium avium-intracellulare complex (MAC) in a 68-year-old woman. Axial CT images (A–C) demonstrate bronchial wall thickening, cylindrical bronchiectasis (arrowheads), endobronchial plugging, and clustered micronodules, greatest in the right middle lobe and lingula. Associated volume loss and opacities due to atelectasis in the inferior lingula are present (*, C). MIP-image (D) shows an increased conspicuity of the “tree-in-bud” morphology of the centrilobular nodules.

THORACIC ENDOMETRIOSIS SYNDROME (TES)

Endometriosis is the abnormal growth of endometrial tissue in extrauterine sites, affecting 10% to 15% of reproductive-age women, most commonly occurring in the abdomen and pelvis.⁶⁵ TES describes the clinical and radiological manifestations resulting from cyclical changes of functional endometrial tissue within the chest, affecting visceral or parietal pleura, lung parenchyma, airways, or diaphragm.⁶⁵ On the basis of the region of involvement, TES is subdivided into the more common pleural form and the less common bronchopulmonary form.⁶⁵ The proposed theories of pleural endometrial implants include retrograde menstruation, microembolization, and common embryological origins of the endometrium, pleural, and peritoneal mesothelium.⁶⁶ The pleural form most often manifests with pneumothorax (73%) and hemothorax (14%).⁶⁵ The bronchopulmonary presents with hemoptysis (7%) and pulmonary nodules (6%).⁶⁶ In both forms, symptoms are temporally related to the onset of menstruation. Catamenial pneumothorax and recurrent pneumothoraces that occur within 24 hours before or 72 hours after the onset of menstruation are the most common manifestation.⁶⁶ On cross-sectional imaging, endometrial implants are frequently located along the posterior and superior right hemidiaphragm (Fig. 13).⁶⁵ On CT, the implants are usually small and hypo-attenuating to iso-attenuating. IV iodinated media increases conspicuity of the diaphragmatic deposits by improving the contrast between the enhancing liver parenchyma and the hypoenhancing endometrial implant.⁶⁵ On MRI, the implants are typically hyperintense on T1-weighted imaging and have a low signal intensity on T2-weighted imaging due to hemorrhage.⁶⁶

FIGURE 13: Thoracic endometriosis syndrome in a 30-year-old woman with cyclical chest pain corresponding with menses. Sagittal lung window (A) and soft tissue window (B) CT images demonstrate a soft tissue attenuation pleural implant along the posterior right hemidiaphragm (arrowheads). A small anterior catamenial pneumothorax is also present (arrows, A). Case courtesy of Seth Kligerman, MD, University of California San Diego.

CHEST WALL AND OSSEOUS ABNORMALITIES

Elastofibroma Dorsi (ED)

ED is a benign hyperplastic fibroelastic lesion of the soft tissues, usually located between the thoracic wall and the lower third of the scapula, under the serratus anterior and latissimus dorsi musculature. ED can be bilateral and may be incidentally discovered on imaging performed for other indications.^67,68 ED has a predilection for females in the fifth to sixth decades of life.^69,70 On CT, the lesions present as a solid mass with ill-defined margins, indistinct to the deep costal plane and separate from the superficial soft tissues by a fat layer (Fig. 14). On MRI, the lesions have better defined margins with a fat plane on both the superficial and deep side without evidence of infiltration into the adjacent tissues or surrounding edema.⁶⁹ They are typically isointense relative to skeletal muscle on both T1-weighted and T2-weighted images with interspersed streaks of fatty tissue with a high signal intensity on T1-weighted and T2-weighted images.⁶⁸ Post-contrast enhancement is variable.⁶⁸ On both CT and MRI, a fasciculated pattern can be helpful in differentiating ED from other tumors. Elastofibromas may show moderate FDG activity on PET/CT exams and should not be mistaken for malignancy when other characteristic imaging features are present.⁶⁷

FIGURE 14: Bilateral ED in a 56-year-old woman. Contrast-enhanced axial CT image demonstrates ill-defined infrascapular soft tissue masses (arrows) with attenuation similar to that of the adjacent chest wall musculature consistent with ED. Case courtesy of Jeffrey Kanne, MD, PhD, University of Wisconsin-Madison.

Osteoporosis (OS) and Insufficiency Fractures

OS, decreased bone mineralization, is influenced by many factors including age, sex, race, hormonal factors, medications, and dietary intake. OS is generally divided into primary and secondary etiologies, with primary OS further divided into postmenopausal and senile types. Postmenopausal OS affects women between the ages of 60 and 65 years, resulting from estrogen deficiency that leads to accelerated bone resorption, preferentially affecting the spine and wrist.⁷¹ Senile OS affects both trabecular and cortical bone, and may manifest as fractures of the hip, proximal humerus, tibia, and pelvis.⁷¹ On radiographs, OS presents with a thin cortex, endosteal resorption, and a decreased number of trabeculae. In the spine, cortical thinning may result in a well-demarcated outline of the vertebral body. Vertebral body compression fractures are the hallmark of OS.⁷¹ It has been estimated that more than one quarter of women aged 65 years and older have one or more vertebral compression fractures.⁷² Thoracic vertebral body compression fractures may lead to progressive kyphosis, which, in turn, can produce a deforming stress on the sternum, resulting in an insufficiency-type stress fracture.⁷³ CT has a greater sensitivity for subtle fractures in comparison with radiographs. MRI is used when suspicion of spinal cord compression or presence of neurologic symptoms is present.⁷⁴

CONCLUSION

Numerous pathologic cardiothoracic processes affect females exclusively, or with increased incidence, in comparison with males. Some of the diseases show distinct sex-based imaging features. In addition, unique female-specific conditions such as pregnancy and lactation require special considerations during the imaging. As such, sex-based differences must be taken into account across radiology, from the choice of imaging modality to the image interpretation.