Journal Logo

Brief Reports

Radial Probe Ultrasound-Guided Cryobiopsy

Berim, Ilya G. MD*; Saeed, Ali I. MD; Awab, Ahmed MD, FCCP; Highley, Adam MD*; Colanta, Agnes MD§; Chaudry, Fawad MBBS

Author Information
Journal of Bronchology & Interventional Pulmonology: April 2017 - Volume 24 - Issue 2 - p 170-173
doi: 10.1097/LBR.0000000000000368
  • Free


Transbronchial cryobiopsy procedure is increasingly utilized in the diagnosis of interstitial lung disease (ILD). Recent medical literature demonstrates higher likelihood of establishing the histologic diagnosis with cryobiopsy when compared with traditional transbronchial forceps biopsy.1 The need for surgical tissue acquisition can be avoided in up to 75% cases with clinical suspicion of ILD.2 However, there is an increased risk of pneumothorax and airway hemorrhage with transbronchial cryobiopsy.3–5 Endobronchial balloon blocker is used by most practitioners to confine potential hemorrhage to affected lobe by inflation of the balloon immediately after removal of the cryoprobe from the segmental airway.5 Radial ultrasound has been utilized to define anatomy of peripheral lung and localization of peripheral pulmonary nodule.6 We herein describe the novel approach of using radial ultrasound to identify at least 1 cm of peribronchial lung parenchyma with low vascularity to minimize risk of hemorrhage during peripheral lung cryobiopsy in patients with suspected ILD.


Single center retrospective review of the electronic medical record was performed with identification of 10 patients undergoing transbronchial cryobiopsies for ILD. Institutional Research Review Board of Creighton University Medical Center approved the study. All patients undergoing peripheral lung cryobiopsy for ILD were included in the study. None of the patients met exclusion criteria, such as patients who are minors or represent vulnerable populations (prisoners, pregnant women, etc.)

Patient Selection and Characteristics

Computed tomography scan of chest was available in all 10 patients to assist the proceduralist in selection of an appropriate area of lung parenchyma for cryobiopsy. General anesthesia with endotracheal intubation was used in all patients. Real-time fluoroscopy was used in all cases to guide the cryobiopsy probe.

Procedures and Equipments

Radial ultrasound probe (Olympus UM-S20-17S) was passed under fluoroscopic guidance into the subsegmental branches of the target lobe and positioned 1 to 2 cm away from pleural surface. Absence of ultrasonographically identifiable vasculature was confirmed (Fig. 1A). The location was marked on fluoroscopy screen (Fig. 2, arrow 1). Ultrasound probe was then slowly withdrawn until pulmonary vasculature was noted (Fig. 1B), at which point the second mark was placed on fluoroscopy screen (Fig. 2, arrow 2). If the distance between the 2 marks was <1 cm as measured during ultrasound probe retraction (Fig. 3), alternative airway was selected and process was repeated. Once the target area for biopsy was established, a 2.4-mm cryoprobe (ERBE 20416-033) was passed through the bronchoscope into the target area. A 3 seconds cryoprobe activation was performed by calling out freeze time by the proceduralist.1 Bronchoscope and cryoprobe were then removed en bloc and the specimen placed in fixative after passive thawing. At the discretion of the operator the process was repeated in different location in the same lobe to achieve up to 3 biopsies. Administration of cold saline, endobronchial blockers, etc., was at the discretion of the proceduralist.

Radial ultrasound images at distal border of hypovascular area (A) and proximal border of hypovascular area (B).
Fluoroscopy screen demonstrating distal border of hypovascular area (arrow 1) and proximal border of hypovascular area (arrow 2).
Illustration of measurement technique for the ultrasound probe withdrawal distance.

Cryobiopsy Bleeding Categorization

Modification of cryobiopsy for ILD with integration of radial probe can decrease the risk for massive bleeding. We herein categorize the severity of bleeding based on intervention required for management after cryobiopsy, modified from previously described scale.1,7 The selection of intervention was at the discretion of proceduralist. Severe bleeding was categorized as termination of procedure with focus on achievement of secured airway.


Cryobiopsy was performed without a peripheral ultrasound guidance in 4 of 10 patients with ILD. One patient had a large hemorrhage (∼300 mL) requiring selective intubation of contralateral main stem bronchus and procedure was stopped for patient safety. Pathology specimen revealed a biopsy of medium-sized pulmonary vessel (Fig. 4) most likely responsible for the extent of the hemorrhage. Endobronchial blocker was used in 1 additional patient. Overall cold saline was administered in 5 patients with no intervention in 2 patients. No large hemorrhage was observed in the radial ultrasound group (6 patients). Cold saline was not administered in 2 of 6 cases (Table 1).

Hematoxylin and eosin stain of cryobiopsy specimen demonstrating medium-sized pulmonary vessel at ×40 magnification (A) and ×100 magnification (B).
List of Hemostatic Interventions


Transbronchial forceps biopsies are performed under fluoroscopy guidance. Recent studies demonstrate that there might be a trend toward more bleeding complications with transbronchial cryobiopsies,1 although severe bleeding requiring surgical intervention has not been reported yet.3 Most proceduralists perform cryobiopsy with placement of balloon blocker positioned proximal to the selected lobe to occlude the segmental airway. The risk of bleeding in patient undergoing transbronchial biopsies is increased with use of therapeutic anticoagulation, antiplatelet therapy (especially clopidogrel), patients with thrombocytopenia, uremia, and clotting factor abnormalities.

If a massive bleed is encountered after cryobiopsy, the management is initiated with immediate attempt to occlude the bleeding airway. Dedicated endobronchial balloon or the bronchoscope itself can be used for this purpose. The patient is then rotated to a lateral position with bleeding side down. Instillation of ice-cold saline can help in achievement of hemostasis by causing cold-induced vascular constriction.8 Intubation or selective intubation of nonbleeding lung is performed in persistent severe bleeding. Patient is then referred to interventional radiology for localization and embolization of the bleeding vessel. Fatality from such hemorrhage is extremely rare, however, has been described previously.9 We herein describe a technique that may decrease amount of hemorrhage during peripheral lung cryobiopsy.

Obviously, no definitive conclusions can be made based on our case series due to small sample size. Conceptually it seems that ability to choose a less vascular area for a somewhat larger cryobiopsy may result in decreased risk of hemorrhage and/or reduction in bleeding severity. Average peripheral cryobiopsy size varies significantly and may be dependent on freezing time and cryoprobe size.4,10,11 Ability to identify a large hypovascular area may add to operator comfort and may allow for longer freezing time and therefore larger biopsy size.11 Impact on procedure duration remains to be determined. Increase in resource utilization due to the use of radial ultrasound could be offset by decrease in complication rate and potentially decreased endobronchial blocker need.

Further development of this approach could include use of a peripheral sheath similar to recently published study12 to ensure that same area is both visualized and biopsied. A multicenter randomized controlled trial is currently under way to evaluate this technique.


1. Pajares V, Puzo C, Castillo D, et al. Diagnostic yield of transbronchial cryobiopsy in interstitial lung disease: a randomized trial. Respirology. 2014;19:900–906.
2. Hagmeyer L, Theegarten D, Treml M, et al. Validation of transbronchial cryobiopsy in interstitial lung disease—interim analysis of a prospective trial and critical review of the literature. Sarcoidosis Vasc Diffuse Lung Dis. 2016;33:2–9.
3. Ravaglia C, Bonifazi M, Wells AU, et al. Safety and diagnostic yield of transbronchial lung cryobiopsy in diffuse parenchymal lung diseases: a comparative study versus video-assisted thoracoscopic lung biopsy and a systematic review of the literature. Respiration. 2016;91:215–227.
4. Babiak A, Hetzel J, Krishna G, et al. Transbronchial cryobiopsy: a new tool for lung biopsies. Respiration. 2009;78:203–208.
5. Poletti V, Casoni GL, Gurioli C, et al. Lung cryobiopsies: a paradigm shift in diagnostic bronchoscopy? Respirology. 2014;19:645–654.
6. Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule. Chest. 2012;142:385–393.
7. Ernst A, Eberhardt R, Wahidi M, et al. Effect of routine clopidogrel use on bleeding complications after transbronchial biopsy in humans. Chest. 2006;129:734–737.
8. Zavala DC. Pulmonary hemorrhage in fiberoptic transbronchial biopsy. Chest. 1976;70:584–588.
9. Papin TA, Lynch JP 3rd, Weg JG. Transbronchial biopsy in the thrombocytopenic patient. Chest. 1985;88:549–552.
10. Kropski JA, Pritchett JM, Mason WR, et al. Bronchoscopic cryobiopsy for the diagnosis of diffuse parenchymal lung disease. PLoS One. 2013;8:e78674.
11. Casoni GL, Tomassetti S, Cavazza A, et al. Transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung diseases. PLoS One. 2014;9:e86716.
12. Yarmus L, Semaan R, Arias S, et al. A randomized controlled trial of a novel sheath cryoprobe for bronchoscopic lung biopsy in a porcine model. Chest. 2016;150:329–336.

cryobiopsy; hemorrhage; radial ultrasound

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.