Lung needle biopsies are among the most common and consequential procedures in interventional radiology. When a radiologist spots a suspicious nodule on a chest scan, the definitive diagnosis usually requires extracting a sliver of tissue through the chest wall, guided by computed tomography. The challenge is geometric as much as medical. The needle must reach the lesion while dodging ribs, avoiding the mediastinum and its great vessels, steering clear of pulmonary fissures, and traversing as little healthy lung parenchyma as possible. Every extra millimeter of lung crossed raises the risk of pneumothorax, the collapsed lung that occurs when air leaks through a puncture, as well as bleeding and hemoptysis. Yet despite decades of advances in imaging, the choice of trajectory still varies considerably from one radiologist to the next, a variability that AI and robotics have long been expected to tame.

The new study, led by Taylor Hoffman and Francois H. Cornelis with colleagues including Stephen B. Solomon and Debkumar Sarkar, set out to test whether a general-purpose generative AI model could shoulder part of that planning burden. The team conducted a retrospective, institutional review board-approved analysis of de-identified CT images from 30 consecutive lung biopsies performed by three interventional radiologists, each with at least a decade of experience. The cohort included 17 men and 13 women with a median age of 65 years, and the lesions ranged from 5 to 45 millimeters across, deliberately spanning technically difficult territory: five apical lesions at the top of the lung, seven subpleural nodules hugging the chest wall, three para-mediastinal lesions, and four near the lung base.

The technical setup was elegantly simple. Each axial CT image, acquired on a GE Healthcare scanner and exported in DICOM format, was cropped and magnified but not rescaled. Using the open-source image editor GIMP, the team overlaid a radial grid on the image and converted it to PNG. One author annotated the target lesion with a blue circle and outlined the sensitive structures in red, including the mediastinum and major vessels. The annotated image was then uploaded to ChatGPT-4 with a standardized prompt specifying five key parameters for an optimal entry angle: reaching the target, minimizing the distance traveled through lung tissue, and avoiding bones, fissures, and the mediastinum. The model was asked to read the radial grid and return the angle at which the needle should enter.

Before running the full analysis, the researchers validated the approach by comparing a pre-biopsy planning CT image with a procedural CT image captured during the actual biopsy, acquired at the same anatomical level and showing the needle, skin, and target in place. A separate validation dataset of 30 paired planning and procedural images was then used for data collection. Each case was processed independently in a fresh chat session, with iterations allowed whenever the model failed to incorporate all criteria. The median number of iterations needed to arrive at a complete answer was just two, with an interquartile range of one to three, suggesting the model could converge on a usable plan with minimal back-and-forth.

The results were striking. Independent reviewers, two experienced interventional radiologists who had not performed the original procedures and who assessed the AI-generated paths in blinded fashion, judged 28 of 30 paths, or 93.3 percent, safe and adequate for performing the biopsy. The two rejected paths were deemed theoretically feasible but not representative of best clinical practice: in one case the AI path crossed 20 millimeters of lung tissue, four times longer than the manual route, and in another it unnecessarily punctured lung parenchyma to reach a subpleural nodule, raising concerns about needle stability. More remarkably, the AI paths crossed a median of just 5 millimeters of lung tissue, compared with 23 millimeters for the paths the human radiologists actually chose, a difference that reached statistical significance with a p-value of 0.0063 on a Wilcoxon signed-rank test. Paths with zero lung traversal corresponded exclusively to subpleural nodules, where a direct pleural puncture enters the lesion immediately.

On the question of whether the AI simply rediscovered what the humans had already chosen, the answer was nuanced. The mean entry angle suggested by the AI was 179 degrees, against 174 degrees for the manual procedures, a difference that was not statistically significant. Using a definition of path match requiring entry angles within 10 degrees of each other and similar trajectories through tissue planes, 8 of 30 cases, or 26.7 percent, showed good concordance. The authors note that this match rate is lower than in earlier work, such as a study by Too and colleagues that used a three-dimensional convolutional neural network for lesion detection and path planning and reported 82 percent concordance with an average angular deviation of 2.30 degrees, alongside 93.5 percent sensitivity and 93.2 percent specificity in lesion detection. That earlier system, however, was purpose-built for the task rather than adapted from a general-purpose chatbot, and it defined path match more narrowly, within 5 degrees.

Why should a shorter path matter? The authors argue that reduced traversal through lung tissue could lessen tissue manipulation and lower the risk of pneumothorax and hemoptysis, potentially shortening procedure time, improving patient comfort, reducing anesthesia use, and increasing operating room efficiency. In the 30 procedures studied, no major complications occurred, and minor events were self-limiting: minimal pneumothorax in four cases, 13.3 percent, which resolved spontaneously, and mild hemoptysis in two cases, 6.7 percent. But the authors also flag a clinical caveat. With a coaxial technique, in which an outer introducer needle anchors the pathway for repeated sampling, a very short path through lung tissue might provide insufficient purchase, increasing the risk that the needle dislodges during the procedure. Shorter, in other words, is not automatically better in every scenario.

The study is candid about its limits. With only 30 cases and a retrospective design, generalizability remains unproven. The analysis was performed in two dimensions on single axial slices rather than in three dimensions, a simplification that may underestimate the true spatial complexity of biopsy planning. The prompt did not require the AI to maintain a standard 5-millimeter safety margin from the subclavian and axillary neurovascular bundles, though those structures were kept out of the imaging field because patients were scanned with their arms raised. Iterative follow-up prompts were not scripted, which limits reproducibility, and the study measured technical feasibility only, not clinical outcomes such as diagnostic yield, complication rates, or procedure time. The authors also caution that GPT-4 itself may soon be superseded, arguing that the field should move toward specialized generative models trained specifically on interventional radiology rather than adapting general-purpose systems.

Even so, the trajectory of the technology is hard to ignore. The authors envision generative AI integrated with robotic biopsy platforms to automate trajectory planning, real-time procedural guidance in which the model continuously analyzes intraoperative imaging and suggests adjustments as the patient moves or breathes, pre-procedural virtual rehearsals that let clinicians simulate multiple approaches before committing to one, and eventual three-dimensional reconstruction that would eliminate manual image annotation altogether. Combined with augmented reality, AI-recommended paths could be projected directly into the clinician’s field of view. The same logic extends beyond the lung to tumor ablation, where precise positioning determines whether the entire tumor is covered, and to vascular interventions, where AI could recommend optimal access routes based on patient-specific anatomy. For now, the message of this small feasibility study is measured but provocative: a model built to converse with humans can, with a radial grid and a well-crafted prompt, plan a needle path through the lung that is measurably less invasive than the one a seasoned specialist picked. The needle, for the moment, remains in human hands, but the map may increasingly be drawn by machines.

Subject of Research: Feasibility of using a multimodal large language model to plan entry angles for CT-guided lung needle biopsies

Article Title: Feasibility study on using multimodal large language model for CT-guided lung biopsy trajectory planning

Article References: Hoffman, T., Worthington, M., Sarkar, D., Solomon, S. B., & Cornelis, F. H. (2025). Feasibility study on using multimodal large language model for CT-guided lung biopsy trajectory planning. CVIR Oncology, 1(1), Article 5. https://doi.org/10.1007/s44343-025-00005-3

Image Credits: AI Generated

DOI: 10.1007/s44343-025-00005-3

Keywords: generative AI, ChatGPT-4, lung biopsy, CT-guided biopsy, trajectory planning, interventional radiology, pneumothorax, needle path planning, multimodal large language model, Memorial Sloan Kettering, CVIR Oncology, medical imaging

The technique at the heart of the consensus, known as US-PLNB, exploits a simple physical fact: sound waves cannot travel through air. That limitation once confined ultrasound to soft tissues like the liver and thyroid, but it becomes an unexpected advantage at the lung’s edge. When a tumor sits directly against the chest wall—the so-called subpleural position—with no aerated lung in between, ultrasound can see it with exquisite clarity, and in real time. Unlike computed tomography, which offers only static snapshots and exposes patients to ionizing radiation, ultrasound shows the needle, the lesion, and the beating, breathing anatomy between them continuously, allowing operators to adjust course millimeter by millimeter. The consensus notes that this real-time capability makes ultrasound particularly valuable for small, mobile lesions near the heart, great vessels, or the lung apex, where a misplaced needle could prove catastrophic.

The document does not pretend ultrasound is a universal solution. Because air blocks sound, the technique applies only to lesions abutting the parietal pleura or to central tumors made visible by surrounding collapse, consolidation, or fluid that creates an acoustic window. CT guidance remains superior for deep and central lesions, offering precise localization at the cost of radiation and longer procedure times. The consensus positions US-PLNB as the first-line method for subpleural lesions, citing reported complication rates of 1.1 to 32.7 percent and safety data consistently favoring ultrasound over CT guidance, including a retrospective series of 3,043 consecutive patients and comparative studies showing shorter wait times and procedure durations.

What distinguishes the new document from prior guidelines, such as those from the British Thoracic Society and the Korean Society of Thoracic Radiology, is its embrace of multimodal ultrasound. Beyond conventional gray-scale imaging, the consensus details how color Doppler imaging maps blood flow within and around a lesion, distinguishing the bidirectional, high-resistance waveform of pulmonary arteries—typical of benign lesions—from the low-resistance bronchial arterial signals and chaotic arteriovenous waveforms that betray malignancy. Elastography adds another dimension: stiff, blue-dominant lesions on strain imaging, or those with shear wave velocities above 2.47 meters per second, are highly likely to be malignant, with reported sensitivity and specificity reaching 98 percent in some series. These tools let operators target the most suspicious, viable regions of a tumor before the needle ever advances.

The most technically sophisticated section concerns contrast-enhanced ultrasound. After an intravenous injection of sulfur hexafluoride microbubbles, malignant lesions typically light up in a snowing-like or curly hair-like pattern as disorganized tumor neovessels fill from the periphery, while benign lesions enhance in a tree-like pattern radiating from the hilum, reflecting preserved pulmonary arterial supply. Because normal lung receives roughly 85 percent of its blood from pulmonary arteries and only 15 percent from bronchial arteries—and because tumors progressively destroy the pulmonary supply in favor of bronchial arteries—the timing of contrast arrival becomes a diagnostic signature. The consensus highlights an arrival-time difference ratio, comparing lesion enhancement against both adjacent lung and chest wall references, that achieved 91 percent diagnostic accuracy at a threshold of 43 percent in published studies. Contrast imaging also reveals necrotic, non-enhancing zones that would yield useless specimens, allowing operators to steer toward viable tissue and reduce false negatives.

Procedural detail in the consensus is granular to the point of being a manual. It specifies that warfarin should be bridged with low-molecular-weight heparin a week before biopsy, aspirin stopped three days ahead, clopidogrel five days ahead, platelets kept above 50 billion per liter, and the international normalized ratio below 1.5. Bevacizumab, the anti-angiogenic drug, must be withheld for roughly four weeks. The document contrasts fine-needle aspiration, which yields cytology with sensitivity of 90 to 95 percent for malignancy, against core needle biopsy, which provides intact histology essential for immunohistochemistry and molecular typing, and recommends combining both to maximize diagnostic yield. Needle selection, firing mechanisms, coaxial techniques that allow multiple samples through a single pleural puncture, and even methods to improve needle visibility on screen—jiggling the needle, injecting saline to outline its track—are all codified.

Complications receive equally rigorous treatment. Hemorrhage, the most common adverse event at 0.3 to 9.9 percent incidence, is managed with a graded protocol from bed rest for minor bleeding through vasopressin and tranexamic acid for moderate hemoptysis to emergency embolization for massive hemorrhage. Pneumothorax, occurring in 0.8 to 11.6 percent of cases, can often be resolved on the spot by aspirating air through the coaxial introducer needle—a maneuver the consensus illustrates with cases in which lesions obscured by escaped air became fully visible again after 20 milliliters were withdrawn. The rarest and deadliest complication, systemic arterial air embolism, carries a mortality of up to 26 percent; the consensus explains that as little as half a milliliter of air in the coronary circulation can be fatal and mandates avoiding aerated bronchi, upright positioning, and positive-pressure ventilation during puncture.

The methodology behind the consensus is as notable as its content. Developed according to the WHO Handbook for Guideline Development and registered on the PREPARE platform, it employed a three-tier structure—a steering committee of five senior experts, a fifteen-member writing group, and a voting panel of nearly one hundred multidisciplinary specialists. Clinical questions were gathered through surveys of more than one hundred physicians, evidence was systematically retrieved from eight Chinese and international databases through August 2025, study quality was assessed with Cochrane, Newcastle-Ottawa, and QUADAS tools, and recommendations were graded using the GRADE framework and ratified through two rounds of anonymous Delphi voting requiring at least 80 percent agreement.

The consensus also looks forward. It endorses image fusion and volume navigation technology, in which electromagnetic sensors track the ultrasound probe and biopsy needle in space, fusing real-time ultrasound with pre-acquired CT volumes to guide biopsies of lesions once considered beyond ultrasound’s reach. The authors acknowledge that large prospective randomized trials directly comparing ultrasound with other guidance modalities are still lacking, and they commit to annual literature monitoring and timely updates as new evidence emerges. For now, the document stands as both a practical manual and a statement of ambition: that a technique once dismissed as too limited for the air-filled lung has matured, with the help of contrast agents, elastography, and navigation systems, into a precise, radiation-free first-line approach for the growing population of patients whose lung lesions sit within reach of a sound wave.

Subject of Research: Development of the first Chinese expert consensus standardizing ultrasound-guided percutaneous lung needle biopsy for subpleural pulmonary lesions

Article Title: Chinese expert consensus on ultrasound-guided percutaneous lung needle biopsy (2025 Edition)

Article References: Wang, Y., Xu, H., & on behalf of Chinese Society of Ultrasound in Medicine, Interventional Physicians Branch of the Chinese Medical Doctor Association, Minimally Invasive Therapy for Oncology Committee of Chinese Anti-Cancer Association, Ultrasound Branch of the Chinese Anti-Tuberculosis Association, Tuberculosis Control and Prevention Branch of the China International Exchange and Promotive Association for Medical and Health Care, Ultrasound Equipment Technology Branch of China Association of Medical Equipment, Ultrasound Su (2026). Chinese expert consensus on ultrasound-guided percutaneous lung needle biopsy (2025 Edition). Clinical Cancer Bulletin, 5(1), Article 4. https://doi.org/10.1007/s44272-026-00055-5

Image Credits: AI Generated

DOI: 10.1007/s44272-026-00055-5

Keywords: ultrasound-guided biopsy, lung biopsy, subpleural pulmonary lesions, expert consensus, contrast-enhanced ultrasound, elastography, interventional ultrasound, pneumothorax, lung cancer diagnosis, image fusion navigation, core needle biopsy, clinical guideline

Her story began fifteen years before the referral that finally cracked the case. Over that period she underwent wedge resections of the right upper lobe, the right lower lobe, and the left upper lobe, each operation removing a wedge of lung tissue in an effort to prevent further collapse. Just two months before she arrived at the pulmonology clinic with exertional breathlessness, she had endured yet another right-sided pneumothorax, this one managed at an outside facility. When clinicians examined her, her vital signs were entirely normal, her lungs sounded clear on auscultation, and crucially, her skin was free of the small papules that might otherwise have pointed toward a diagnosis. Laboratory investigations, including a complete blood count, renal function tests, liver enzymes, D-dimer, inflammatory markers, and a broad panel of autoimmune antibodies, all came back unremarkable. Pulmonary function testing showed only mild reductions in airflow and lung capacity, with an FEV1/FVC ratio of 0.89, an FEV1 of 81 percent predicted, a forced vital capacity of 79 percent predicted, and a total lung capacity of 99 percent predicted.

The turning point came with chest computed tomography. The scan revealed multiple bilateral pulmonary cysts, thin-walled air-filled spaces scattered through both lungs, with a telling pattern: they clustered predominantly in the lower lobes and in the medial, or central, zones of the lung. That distribution matters, because it is a signature that experienced thoracic radiologists associate with a specific and rare genetic syndrome rather than with the more common cystic lung diseases. The differential diagnosis for diffuse cystic lung disease is short but consequential, encompassing lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis, and lymphoid interstitial pneumonia. Each mimics the others on imaging, yet each carries a profoundly different prognosis and management pathway, which is why distinguishing among them is one of the most intellectually demanding puzzles in pulmonary medicine.

The clinical team methodically eliminated the alternatives. The patient had never smoked, which argued strongly against pulmonary Langerhans cell histiocytosis, a disease overwhelmingly linked to cigarette use. Her unremarkable autoimmune serologies made lymphoid interstitial pneumonia, which typically arises in the context of autoimmune or systemic disease, unlikely as well. That left lymphangioleiomyomatosis, known as LAM, as the chief suspect. To resolve the question, the researchers went back to tissue that had been sitting in the pathology archive for years: the specimens from her prior wedge resections. Under the microscope, the lung tissue showed multiple subpleural and parenchymal cystic spaces lined by flattened epithelium, with the surrounding non-cystic lung appearing unremarkable. Immunohistochemical staining for HMB-45 and GPNMB, two molecular markers that light up in LAM, came back negative, formally excluding that diagnosis and narrowing the field dramatically.

With the imaging pattern pointing in one direction and the mimics ruled out, suspicion settled on Birt-Hogg-Dubé syndrome, an extraordinarily rare autosomal dominant disorder caused by pathogenic germline variants in the FLCN gene. The syndrome’s estimated prevalence ranges from roughly 2 in 1,000,000 to 1 in 200,000, affecting men and women equally, and experts believe the true figure is almost certainly higher because so many cases go unrecognized. Classically, the disorder is described as a triad of cutaneous fibrofolliculomas, benign hair-follicle tumors on the face, neck, and upper trunk; bilateral pulmonary cysts; and renal tumors. But as this case demonstrates vividly, the textbook triad is not the whole story. Pulmonary manifestations are among the most prevalent features of Birt-Hogg-Dubé syndrome, and they can occur entirely in isolation, without any skin lesions or kidney tumors to alert clinicians to the genetic basis of the disease.

To confirm the diagnosis, the team performed germline whole-exome sequencing, a technology that reads the protein-coding regions of a patient’s entire genome. The analysis identified a heterozygous frameshift variant in the FLCN gene, designated NM_144997.7:c.1579_1580insA, resulting in a truncated protein labeled p.Arg527GlnfsTer75. Under American College of Medical Genetics and Genomics guidelines, the variant was classified as pathogenic, delivering a definitive molecular diagnosis of Birt-Hogg-Dubé syndrome. Formal dermatologic evaluation subsequently found no fibrofolliculomas, and abdominal imaging showed no renal tumors, cementing the conclusion that this was an isolated pulmonary presentation of the disease. Formal genetic counseling followed, in which the patient learned about the autosomal dominant inheritance pattern, meaning each of her children has a fifty percent chance of carrying the same mutation. Cascade genetic testing was offered to her first-degree relatives, and she was enrolled in annual renal surveillance using magnetic resonance imaging, a precaution taken because of the lifetime risk of kidney malignancy that accompanies the syndrome.

At the molecular level, the story of Birt-Hogg-Dubé syndrome is a story about a tumor suppressor gone missing. The FLCN gene encodes folliculin, a protein that regulates mTORC1, a master cellular signaling complex that controls growth, metabolism, and proliferation. When loss-of-function variants disable folliculin, mTORC1 activity becomes dysregulated, and evidence from human Birt-Hogg-Dubé tissue and mouse models implicates this deranged signaling in the formation of the alveolar cysts that weaken the lung and predispose carriers to spontaneous pneumothorax. In other words, the same genetic lesion that raises the specter of kidney cancer also, through a distinct downstream pathway, slowly riddles the lungs with fragile air spaces that can rupture without warning, collapsing the lung and squeezing it away from the chest wall.

The epidemiology of the pulmonary disease underscores why early recognition is so valuable. Spontaneous pneumothorax develops in approximately 30 to 50 percent of patients with Birt-Hogg-Dubé syndrome, typically at a median onset age of 30 to 38 years, and it recurs frequently, exactly as it did in this patient over a decade and a half. The cysts themselves have characteristic features on imaging: they tend to be thin-walled and lentiform, meaning lens-shaped or oval, and they favor the lower lobes and medial lung zones, in contrast to the upper-lobe and peripheral distribution seen in many other cystic lung diseases. Diagnostic criteria for the syndrome require either one major criterion, such as at least five fibrofolliculomas or a pathogenic FLCN variant, or two minor criteria, which include unexplained bilateral pulmonary cysts, early-onset multifocal renal tumors before the age of 50, or a first-degree relative with the syndrome. Perhaps the most sobering statistic attached to the disease is the diagnostic lag: the mean delay from symptom onset to diagnosis has been reported at more than seven years, a window in which patients may undergo repeated chest tubes, repeated surgeries, and repeated collapses without ever learning that a single inherited gene variant lies at the root of it all.

For now, there is no approved disease-modifying therapy for Birt-Hogg-Dubé syndrome, which makes surveillance and prevention the cornerstones of care. Acute pneumothorax is managed with standard approaches, and for patients with recurrent episodes, as in this case, surgical intervention or pleurodesis, a procedure that adheres the lung to the chest wall to prevent future collapse, should be considered. Because renal malignancy, though typically indolent, is the most serious complication of the syndrome, lifelong annual renal surveillance with MRI beginning at age 20 is recommended, allowing tumors to be detected while they are small and treatable. Patients are strongly advised never to smoke, since smoking compounds the threat to already vulnerable lungs. And as this case makes clear, the reach of a diagnosis extends beyond the individual patient: cascade genetic testing of first-degree relatives is essential to identify asymptomatic carriers before cysts form, lungs collapse, or kidney tumors develop. For a woman who spent fifteen years in a cycle of collapse and surgery, a single blood test grounded in a sharp radiological eye finally delivered an answer, a management plan, and a warning that may protect her entire family.

Subject of Research: Birt-Hogg-Dubé syndrome presenting with isolated pulmonary manifestations causing recurrent spontaneous pneumothorax

Article Title: An Underrecognized Cause of Recurrent Spontaneous Pneumothorax: Birt‐Hogg‐Dubé Syndrome With Isolated Pulmonary Manifestation

Article References: An Underrecognized Cause of Recurrent Spontaneous Pneumothorax: Birt‐Hogg‐Dubé Syndrome With Isolated Pulmonary Manifestation. (n.d.). https://doi.org/10.1002/rcr2.70703

Image Credits: AI Generated

DOI: 10.1002/rcr2.70703

Keywords: Birt-Hogg-Dubé syndrome, FLCN gene, pneumothorax, cystic lung disease, folliculin, mTORC1 signaling, genetic testing, lymphangioleiomyomatosis, renal surveillance, whole-exome sequencing, pulmonary cysts, rare disease