Safety and efficacy of histotripsy delivery through overlying gas-filled small bowel in an ex vivo swine model.

PURPOSE: To evaluate the safety and efficacy of performing histotripsy through overlying gas-filled bowel in an ex vivo swine model. METHODS: An ex vivo model was created to simulate histotripsy treatment of solid organs through gas-filled bowel. Spherical 2.5 cm histotripsy treatments were performed in agar phantoms for each of five treatment groups: 1) control with no overlying bowel (n = 6), 2) bowel 0 cm above phantom (n = 6), 3) bowel 1 cm above phantom (n = 6), 4) bowel 2 cm above phantom (n = 6), and 5) bowel 0 cm above the phantom with increased treatment amplitude (n = 6). Bowel was inspected for gross and microscopic damage, and treatment zones were measured. A ray-tracing simulation estimated the percentage of therapeutic beam path blockage by bowel in each scenario. RESULTS: All histotripsy treatments through partial blockage were successful (24/24). No visible or microscopic damage was observed to intervening bowel. Partial blockage resulted in a small increase in treatment volume compared to controls (p = 0.002 and p = 0.036 for groups with bowel 0 cm above the phantom, p > 0.3 for bowel 1 cm and 2 cm above the phantom). Gas-filled bowel was estimated to have blocked 49.6%, 35.0%, and 27.3% of the therapeutic beam at 0, 1, and 2 cm, respectively. CONCLUSION: Histotripsy has the potential to be applied through partial gas blockage of the therapeutic beam path, as shown by this ex vivo small bowel model. Further work in an in vivo survival model appears indicated.

Unreimbursed Costs of Multidisciplinary Conferences to a Radiology Department: A Prospective Analysis at an Academic Medical Center.

PURPOSE: Multidisciplinary conferences (MDCs) are important for clinical care but are unreimbursed and can be time-consuming for radiologists to prepare for and present. The purpose of this single-center, prospective, survey-based study is to measure the per-conference time and total time radiologists devote to MDCs at a single academic medical center. Secondary objectives are to determine the source of radiologist preparation time, and calculate the per conference and overall radiology departmental costs of MDC participation. METHODS: A prospective survey was performed to capture all radiology preparation and presentation time for MDCs in a 3-month period, which was then annualized. Total cost was calculated on the basis of Association of Administrators in Academic Radiology survey data for nonchair academic radiologist compensation plus a 30% fringe-benefit rate. RESULTS: The survey response rate was 86.9%. A total of 3,358 hours were devoted annually to MDCs, which represents time equivalent to 1.9 full-time equivalents or $1,155,152 in unreimbursed radiology departmental costs. Per-MDC total preparation and presentation time was 2.7 hours, at an annual cost of $46,440 for each weekly MDC. Radiologists used a combination of personal time (49.7%), academic time (42%), and/or clinical time (35.4%) to prepare for MDCs. Radiologists devoted a mean of 47.9 hours (1.2 weeks) of time per annum to MDCs. CONCLUSIONS: Radiologist time devoted to MDCs at the survey institution was substantial, and preparation time was drawn disproportionately from personal and academic time, which may have negative implications for burnout, recruitment and retention, and academic productivity unless it is effectively mitigated.

CT Navigation for Percutaneous Needle Placement: How I Do It.

CT navigation (CTN) has recently been developed to combine many of the advantages of conventional CT and CT-fluoroscopic guidance for needle placement. CTN systems display real-time needle position superimposed on a CT dataset. This is accomplished by placing electromagnetic (EM) or optical transmitters/sensors on the patient and needle, combined with fiducials placed within the scan field to superimpose a known needle location onto a CT dataset. Advantages of CTN include real-time needle tracking using a contemporaneous CT dataset with the patient in the treatment position, reduced radiation to the physician, facilitation of procedures outside the gantry plane, fewer helical scans during needle placement, and needle guidance based on diagnostic-quality CT datasets. Limitations include the display of a virtual (vs actual) needle position, which can be inaccurate if the needle bends, the fiducial moves, or patient movement occurs between scans, and limitations in anatomical regions with a high degree of motion such as the lung bases. This review summarizes recently introduced CTN technologies in comparison to historical methods of CT needle guidance. A "How I do it" section follows, which describes how CT navigation has been integrated into the study center for both routine and challenging procedures, and includes step-by-step explanations, technical tips, and pitfalls.

Artificial Intelligence-Aided Selection of Needle Pathways: Proof-of-Concept in Percutaneous Lung Biopsies.

PURPOSE: To evaluate the concordance between lung biopsy puncture pathways determined by artificial intelligence (AI) and those determined by expert physicians. MATERIALS AND METHODS: An AI algorithm was created to choose optimal lung biopsy pathways based on segmented thoracic anatomy and emphysema in volumetric lung computed tomography (CT) scans combined with rules derived from the medical literature. The algorithm was validated using pathways generated from CT scans of randomly selected patients (n = 48) who had received percutaneous lung biopsies and had noncontrast CT scans of 1.25-mm thickness available in picture archiving and communication system (PACS) (n = 28, mean age, 68.4 years ± 9.2; 12 women, 16 men). The algorithm generated 5 potential pathways per scan, including the computer-selected best pathway and 4 random pathways (n = 140). Four experienced physicians rated each pathway on a 1-5 scale, where scores of 1-3 were considered safe and 4-5 were considered unsafe. Concordance between computer and physician ratings was assessed using Cohen's κ. RESULTS: The algorithm ratings were statistically equivalent to the physician ratings (safe vs unsafe: κ¯=0.73; ordinal scale: κ¯=0.62). The computer and physician ratings were identical in 57.9% (81/140) of cases and differed by a median of 0 points. All least-cost "best" pathways generated by the algorithm were considered safe by both computer and physicians (28/28) and were judged by physicians to be ideal or near ideal. CONCLUSIONS: AI-generated lung biopsy puncture paths were concordant with expert physician reviewers and considered safe. A prospective comparison between computer- and physician-selected puncture paths appears indicated in addition to expansion to other anatomic locations and procedures.

Clinical translation of abdominal histotripsy: a review of preclinical studies in large animal models.

Histotripsy is an emerging noninvasive, non-thermal, and non-ionizing focused ultrasound (US) therapy that can be used to destroy targeted tissue. Histotripsy has evolved from early laboratory prototypes to clinical systems which have been comprehensively evaluated in the preclinical environment to ensure safe translation to human use. This review summarizes the observations and results from preclinical histotripsy studies in the liver, kidney, and pancreas. Key findings from these studies include the ability to make a clinically relevant treatment zone in each organ with maintained collagenous architecture, potentially allowing treatments in areas not currently amenable to thermal ablation. Treatments across organ capsules have proven safe, including in anticoagulated models which may expand patients eligible for treatment or eliminate the risk associated with taking patients off anti-coagulation. Treatment zones are well-defined with imaging and rapidly resorb, which may allow improved evaluation of treatment zones for residual or recurrent tumor. Understanding the effects of histotripsy in animal models will help inform physicians adopting histotripsy for human clinical use.

A Comparison of Histotripsy and Percutaneous Cryoablation in a Chronic Healthy Swine Kidney Model.

PURPOSE: To compare the safety and efficacy of histotripsy with cryoablation in a chronic human-scale normal porcine kidney model. MATERIALS AND METHODS: Eighteen female domestic swine were divided evenly into histotripsy and cryoablation treatment arms. A planned 2-3 cm diameter treatment was performed under ultrasound (histotripsy) or ultrasound and computed tomography (CT) guidance (cryoablation). Contrast-enhanced CT and serum blood analysis were performed immediately postprocedure and on day 7, with either immediate killing (n = 3) or continued survival to day 30 (n = 6), at which time contrast-enhanced CT, serum blood analysis, and necropsy were performed. Animal welfare, treatment zone appearance, procedure-related adverse events, and histopathology of the treatment zones and surrounding tissues were assessed. RESULTS: Histotripsy treatment zones (mean ±standard deviation diameters, 2.7 ± 0.12 × 2.4 ± 0.19 × 2.4 ± 0.26 cm; volume, 8.3 ± 1.9 cm3) were larger than cryoablation zones (mean diameters, 2.2 ± 0.19 × 1.9 ± 0.13 × 1.7 ± 0.19 cm; volume, 3.9 ± 0.8 cm3; P < .001). At 30 days, histotripsy and cryoablation treatment zone volumes decreased by 96% and 83% on CT, respectively (P < .001). Perirenal hematomas were present after 8 of 9 (89%) cryoablation (mean volume, 22.2 cm3) and 1 of 9 (11%, P < .001) histotripsy (volume, 0.4 cm3) procedures, with active arterial extravasation in 4 of 9 (44%) cryoablation and no histotripsy animals (P = .206). All 9 histotripsy animals and 5 of 9 (56%) cryoablation animals had collecting system debris (P = .042). Changes in serum creatinine were similar between the groups (P = .321). CONCLUSIONS: Other than a higher rate of bleeding after cryoablation, the safety and early efficacy of histotripsy and cryoablation were comparable for creating treatment zones in a chronic normal porcine kidney model.

Percutaneous CT-Guided Abdominal and Pelvic Biopsies: Comparison of an Electromagnetic Navigation System and CT Fluoroscopy.

PURPOSE: To compare electromagnetic navigation (EMN) with computed tomography (CT) fluoroscopy for guiding percutaneous biopsies in the abdomen and pelvis. MATERIALS AND METHODS: A retrospective matched-cohort design was used to compare biopsies in the abdomen and pelvis performed with EMN (consecutive cases, n = 50; CT-Navigation; Imactis, Saint-Martin-d'Hères, France) with those performed with CT fluoroscopy (n = 100). Cases were matched 1:2 (EMN:CT fluoroscopy) for target organ and lesion size (±10 mm). RESULTS: The population was well-matched (age, 65 vs 65 years; target size, 2.0 vs 2.1 cm; skin-to-target distance, 11.4 vs 10.7 cm; P > .05, EMN vs CT fluoroscopy, respectively). Technical success (98% vs 100%), diagnostic yield (98% vs 95%), adverse events (2% vs 5%), and procedure time (33 minutes vs 31 minutes) were not statistically different (P > .05). Operator radiation dose was less with EMN than with CT fluoroscopy (0.04 vs 1.2 µGy; P < .001), but patient dose was greater (30.1 vs 9.6 mSv; P < .001) owing to more helical scans during EMN guidance (3.9 vs 2.1; P < .001). CT fluoroscopy was performed with a mean of 29.7 tap scans per case. In 3 (3%) cases, CT fluoroscopy was performed with gantry tilt, and the mean angle out of plane for EMN cases was 13.4°. CONCLUSIONS: Percutaneous biopsies guided by EMN and CT fluoroscopy were closely matched for technical success, diagnostic yield, procedure time, and adverse events in a matched cohort of patients. EMN cases were more likely to be performed outside of the gantry plane. Radiation dose to the operator was higher with CT fluoroscopy, and patient radiation dose was higher with EMN. Further study with a wider array of procedures and anatomic locations is warranted.

Kinetic Measurements Reveal Enhanced Protein-Protein Interactions at Intercellular Junctions.

The binding properties of adhesion proteins are typically quantified from measurements with soluble fragments, under conditions that differ radically from the confined microenvironment of membrane bound proteins in adhesion zones. Using classical cadherin as a model adhesion protein, we tested the postulate that confinement within quasi two-dimensional intercellular gaps exposes weak protein interactions that are not detected in solution binding assays. Micropipette-based measurements of cadherin-mediated, cell-cell binding kinetics identified a unique kinetic signature that reflects both adhesive (trans) bonds between cadherins on opposing cells and lateral (cis) interactions between cadherins on the same cell. In solution, proposed lateral interactions were not detected, even at high cadherin concentrations. Mutations postulated to disrupt lateral cadherin association altered the kinetic signatures, but did not affect the adhesive (trans) binding affinity. Perturbed kinetics further coincided with altered cadherin distributions at junctions, wound healing dynamics, and paracellular permeability. Intercellular binding kinetics thus revealed cadherin interactions that occur within confined, intermembrane gaps but not in solution. Findings further demonstrate the impact of these revealed interactions on the organization and function of intercellular junctions.