Technical note: A comparison of physician doses in C-Arm and CT fluoroscopy procedures.

PURPOSE: We address the misconception that the typical physician dose is higher for CT fluoroscopy (CTF) procedures compared to C-Arm procedures. METHODS: We compare physician scatter doses using two methods: a literature review of reported doses and a model based on a modified form of the dose area product (DAP). We define this modified form of DAP, "cumulative absorbed DAP," as the product of the area of the x-ray beam striking the patient, the dose rate per unit area, and the exposure time. RESULTS: The patient entrance dose rate for C-Arm fluoroscopy (0.2 mGy/s) was found to be 15 times lower than for CT fluoroscopy (3 mGy/s). A typical beam entrance area for C-Arm fluoroscopy reported in the literature was found to be 10.6 × 10.6 cm (112 cm2), whereas for CTF was 0.75 × 32 cm (24 cm2). The absorbed DAP rate for C-Arm fluoroscopy (22 mGy*cm2/s) was found to be 3.3 times lower than for CTF (72 mGy*cm2/s). The mean fluoroscopy time for C-Arm procedures (710 s) was found to be 21 times higher than for CT fluoroscopy procedures (23 s). The cumulative absorbed DAP for C-Arm procedures was found to be 9.4 times higher when compared to CT procedures (1.59 mGy*m2 vs. 0.17 mGy*m2). CONCLUSIONS: The higher fluoroscopy time in C-Arm procedures leads to a much lower cumulative DAP (i.e., physician scatter dose) in CTF procedures. This result can inform interventional physicians deciding on whether to perform inter-procedural imaging inside the room as opposed to retreating from the room.

Revealing the algicidal characteristics of Maribacter dokdonensis: An investigation into bacterial strain P4 isolated from Karenia mikimotoi bloom water.

Harmful algal blooms (HABs) are a global environmental concern, causing significant economic losses in fisheries and posing risks to human health. Algicidal bacteria have been suggested as a potential solution to control HABs, but their algicidal efficacy is influenced by various factors. This study aimed to characterize a novel algicidal bacterium, Maribacter dokdonensis (P4), isolated from a Karenia mikimotoi (Hong Kong strain, KMHK) HAB and assess the impact of P4 and KMHK's doses, growth phase, and algicidal mode and the axenicity of KMHK on P4's algicidal effect. Our results demonstrated that the algicidal effect of P4 was dose-dependent, with the highest efficacy at a dose of 25% v/v. The study also determined that P4's algicidal effect was indirect, with the P4 culture and the supernatant, but not the bacterial cells, showing significant effects. The algicidal efficacy was higher when both P4 and KMHK were in the stationary phase. Furthermore, the P4 culture at the log phase could effectively kill KMHK cells at the stationary phase, with higher algicidal efficacy in the bacterial culture than that of the supernatant alone. Interestingly, P4's algicidal efficacy was significantly higher when co-culturing with xenic KMHK (~90% efficacy at day 1) than that with the axenic KMHK (~50% efficacy at day 1), suggesting the presence of other bacteria could regulate P4's algicidal effect. The bacterial strain P4 also exhibited remarkable algicidal efficacy on four other dinoflagellate species, particularly the armored species. These results provide valuable insights into the algicidal effect of M. dokdonensis on K. mikimotoi and on their interactions.

Needle artifact reduction during interventional CT procedures using a silver filter.

BACKGROUND: MAR algorithms have not been productized in interventional imaging because they are too time-consuming. Application of a beam hardening filter can mitigate metal artifacts and doesn't increase computational burden. We evaluate the ability to reduce metal artifacts of a 0.5 mm silver (Ag) additional filter in a Multidetector Computed Tomography (MDCT) scanner during CT-guided biopsy procedures. METHODS: A biopsy needle was positioned inside the lung field of an anthropomorphic phantom (Lungman, Kyoto Kagaku, Kyoto, Japan). CT acquisitions were performed with beam energies of 100 kV, 120 kV, 135 kV, and 120 kV with the Ag filter and reconstructed using a filtered back projection algorithm. For each measurement, the CTDIvol was kept constant at 1 mGy. Quantitative profiles placed in three regions of the artifact (needle, needle tip, and trajectory artifacts) were used to obtain metrics (FWHM, FWTM, width at - 100 HU, and absolute error in HU) to evaluate the blooming artifact, artifact width, change in CT number, and artifact range. An image quality analysis was carried out through image noise measurement. A one-way analysis of variance (ANOVA) test was used to find significant differences between the conventional CT beam energies and the Ag filtered 120 kV beam. RESULTS: The 120 kV-Ag is shown to have the shortest range of artifacts compared to the other beam energies. For needle tip and trajectory artifacts, a significant reduction of - 53.6% (p < 0.001) and - 48.7% (p < 0.001) in the drop of the CT number was found, respectively, in comparison with the reference beam of 120 kV as well as a significant decrease of up to - 34.7% in the artifact width (width at - 100 HU, p < 0.001). Also, a significant reduction in the blooming artifact of - 14.2% (FWHM, p < 0.001) and - 53.3% (FWTM, p < 0.001) was found in the needle artifact. No significant changes (p > 0.05) in image noise between the conventional energies and the 120 kV-Ag were found. CONCLUSIONS: A 0.5 mm Ag additional MDCT filter demonstrated consistent metal artifact reduction generated by the biopsy needle. This reduction may lead to a better depiction of the target and surrounding structures while maintaining image quality.

Percutaneous Microwave Ablation for Treatment of Retroperitoneal Tumors.

Purpose To determine if microwave ablation (MWA) of retroperitoneal tumors can safely provide high rates of local tumor control. Materials and Methods This retrospective study included 19 patients (median age, 65 years [range = 46-78 years]; 13 [68.4%] men and six [31.6%] women) with 29 retroperitoneal tumors treated over 22 MWA procedures. Hydrodissection (0.9% saline with 2% iohexol) was injected in 17 of 22 (77.3%) procedures to protect nontarget anatomy. The primary outcomes evaluated were local tumor progression (LTP) and complication rates. Oncologic outcomes, including overall survival (OS), progression-free survival (PFS), and treatment-free interval (TFI), were examined as secondary outcome measures. Results Median follow-up was 18 months (range = 0.5-113). Hydrodissection was successful in displacing nontarget anatomy in 16 of 17 (94.1%) procedures. The LTP rate was 3.4% (one of 29; 95% CI: 0.1, 17.8) per tumor and 5.3% (one of 19; 95% CI: 0.1, 26.0) per patient. The overall complication rate per patient was 15.8% (three of 19), including two minor complications and one major complication. The OS rate at 1, 2, and 3 years was 81.8%, 81.8%, and 72.7%, respectively, with a median OS estimated at greater than 7 years. There was no evidence of a difference in OS (P = .34) and PFS (P = .56) between patients with renal cell carcinoma (six of 19 [31.6%]) versus other tumors (13 of 19 [68.4%]) and patients treated with no evidence of disease (15 of 22 [68.2%]) versus patients with residual tumors (seven of 22 [31.8%]). Median TFI was 18 months (range = 0.5-108). Conclusion Treatment of retroperitoneal tumors with MWA combined with hydrodissection provided high rates of local control, prolonged systemic therapy-free intervals, and few serious complications. Keywords: Ablation Techniques (ie, Radiofrequency, Thermal, Chemical), Retroperitoneum, Microwave Ablation, Hydrodissection © RSNA, 2024.

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.

A retrospective study of outcomes and the validation of the Sheffield Gastrostomy Score in PEGs, RIGs and PIGs.

INTRODUCTION: There are limited studies comparing the safety and effectiveness of Radiologically Assisted Gastrostomies (RAGs) against Percutaneous Endoscopic Gastrostomies (PEGs). The Sheffield Gastrostomy Score (SGS) can be used to help predict 30-day mortality, more information is needed on its validity in RAGs. Our aim is to compare mortality between RAGs (Radiologically Inserted Gastrostomies (RIGs) and Per-oral Image Guided Gastrostomies (PIGs)) with PEGs and validate the SGS. METHOD: Data on gastrostomies newly inserted in three hospitals from 2016-2019 were retrospectively collected. Demographics, indication, insertion date, date of death, inpatient status and blood tests (albumin, CRP and eGFR) were recorded. RESULTS: 1977 gastrostomies were performed: Gastrostomy mortality at 7 days was 1.3% and at 30 days was 6%. There was a 5% 30-day mortality for PEGs, 5.5% RIGs, 7.2% PIGs (p = 0.215). Factors increasing 30 day mortality were age ≥60 years (p = 0.039), albumin <35 g/L (p = 0.005), albumin <25 g/L (p < 0.001) and CRP ≥10 mg/L (p < 0.001). For patients who died within 30 days; 0.6% had an SGS of 0, 3.7% = 1, 10.2% = 2 and 25.5% = 3, with similar trends for RAGs and PEGs. ROC curves showed the area under the curve for all gastrostomies, RAGs and PEGs as 0.743, 0.738, 0.787 respectively. DISCUSSION: There was no significant difference between 30-day mortality for PEGs, RIGs and PIGs. Factors predicting risk include age ≥60 years, albumin <35 g/L, albumin <25 g/L and CRP ≥10 mg/L. The SGS has been validated in this study for PEGs and for the first time in RAGs as well..

Intra- and inter-habitat variation in sediment heavy metals, antibiotics and ecological risks in Mai Po RAMSAR, China.

Distribution of heavy metals (HMs) and antibiotics (ABs) in surface sediments of three habitats: mudflat, mangrove and gei wai (inter-tidal shrimp ponds), at Mai Po RAMSAR were determined with inductively coupled plasma and liquid chromatograph tandem - mass spectrometry, respectively. Eight HMs (Cr, As, Pb, Cd, Mn, Ni, Cu and Zn), and ten ABs (tetracyclines, quinolones, macrolides and sulphonamides) were detected in all habitats, with relatively lower concentration in gei wai. Ecological risk assessment based on PNEC revealed that HMs posed a higher ecological risk to microorganisms than ABs. All metals except Mn were above their respective threshold effect levels according to sediment quality guidelines, indicating their potential toxicity to benthos. The enrichment factor and geo-accumulation index on background values suggested sediments were moderately polluted by Zn, Cu and Cd, possibly from anthropogenic inputs. This study implies that HMs pollution must be prevented through proper regulation of agricultural and industrial discharge.

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.

Upregulation of Peridinin-Chlorophyll A-Binding Protein in a Toxic Strain of Prorocentrum hoffmannianum under Normal and Phosphate-Depleted Conditions.

Some strains of the dinoflagellate species Prorocentrum hoffmannianum show contrasting ability to produce diarrhetic shellfish poisoning (DSP) toxins. We previously compared the okadaic acid (OA) production level between a highly toxic strain (CCMP2804) and a non-toxic strain (CCMP683) of P. hoffmannianum and revealed that the cellular concentration of OA in CCMP2804 would increase significantly under the depletion of phosphate. To understand the molecular mechanisms, here, we compared and analyzed the proteome changes of both strains growing under normal condition and at phosphate depletion using two-dimensional gel electrophoresis (2-DE). There were 41 and 33 differential protein spots observed under normal condition and phosphate depletion, respectively, of which most were upregulated in CCMP2804 and 22 were common to both conditions. Due to the lack of matched peptide mass fingerprints in the database, de novo peptide sequencing was applied to identify the differentially expressed proteins. Of those upregulated spots in CCMP2804, nearly 60% were identified as peridinin-chlorophyll a-binding protein (PCP), an important light-harvesting protein for photosynthesis in dinoflagellates. We postulated that the high expression of PCP encourages the production of DSP toxins by enhancing the yields of raw materials such as acetate, glycolate and glycine. Other possible mechanisms of toxicity related to PCP might be through triggering the transcription of non-ribosomal peptide synthetase/polyketide synthase genes and the transportation of dinophysistoxin-4 from chloroplast to vacuoles.

Hepatic and Renal Histotripsy in an Anticoagulated Porcine Model.

PURPOSE: To determine the risk of mechanical vessel wall damage resulting in hemorrhage during and after hepatic and renal histotripsy in an anticoagulated in vivo porcine model. MATERIALS AND METHODS: Non-tumor-bearing pigs (n = 8; mean weight, 52.5 kg) were anticoagulated with warfarin (initial dose, 0.08 mg/kg) to a target prothrombin time (PT) of 30%-50% above baseline. A total of 15 histotripsy procedures were performed (kidney: n = 8, 2.0-cm sphere; liver: n = 7, 2.5-cm sphere). Treatments were immediately followed by computed tomography (CT) imaging. Animals were observed for 7 days while continuing anticoagulation, followed by repeat CT and necropsy. RESULTS: All animals survived to complete the entire protocol with no signs of disability or distress. Three animals had hematuria (pink urine without clots). Baseline PT values (mean, 16.0 seconds) were elevated to 22.0 seconds (37.5% above baseline, P = .003) on the day of treatment and to 28.8 seconds (77.8% above baseline, P < .001) on the day of necropsy. At the time of treatment, 5 of 8 (63%) animals were at a therapeutic anticoagulation level, and all 8 animals (100%) reached therapeutic levels by the time of necropsy. There were no cases of intraparenchymal, peritoneal, or retroperitoneal hemorrhage associated with any treatments despite 5 of 7 (71%) liver and all 8 (100%) kidney treatments extending to the organ surface. CONCLUSIONS: Liver and kidney histotripsy seems safe with no elevated bleeding risk in this anticoagulated animal model, supporting the possibility of histotripsy treatments in patients on anticoagulation.

Histotripsy of Subcutaneous Fat in a Live Porcine Model.

PURPOSE: This study was designed to evaluate the feasibility and safety of histotripsy subcutaneous (SQ) fat treatment in an in-vivo porcine model, and evaluate evolution of the treated volume on MRI and pathology. METHODS/MATERIALS: 10 histotripsy SQ fat treatments were completed in 5 swine, divided into four groups based on pre-determined survival: day 0 (n = 4), day 7 (n = 2), day 28 (n = 2), and day 56 (n = 2). A 4.0 × 4.0x2.0 cm ovoid treatment was created in the fat pad of the posterior thorax. MRI of survived animals were obtained on day 7 (n = 6), day 28 (n = 4), and day 56 (n = 2), and reviewed for size and imaging characteristics. Technical success was defined as the creation of a treatment zone in the targeted SQ fat. Skin firmness and indentation were qualitatively scored. RESULTS: Histotripsy had a 100% (10/10) technical success for creation of SQ fat treatments. Mean treatment time was 35.5 min (range 35-36.5). The volume of treated SQ fat demonstrated 92% volume reduction over the study. Day 0 gross pathology treatment had a mean volume of 12.6 cm3 (± 2.1) (prescribed volume of 16.7 cm3), which decreased to 8.3 cm3 (± 2.8) by day 7 (34% overall decrease), 3.0 cm3 (± 0.5) by day 28 (76% overall decrease), and 1.0 cm3 (± 1.2) by day 56 (92% overall decrease). Mean firmness and indentation scores showed no change from baseline at all time points, with no overlying skin injury. CONCLUSION: Histotripsy safely and effectively treated SQ fat of an in-vivo porcine model, with volume reduction over time.

A comparison study of microwave ablation vs. histotripsy for focal liver treatments in a swine model.

OBJECTIVE: To compare the acute and chronic safety and treatment effects of non-invasive hepatic histotripsy vs. percutaneous microwave (MW) ablation in a healthy porcine model. METHODS: This was a dual-arm study in which each animal (n = 14) received either a single hepatic microwave (n = 6) or histotripsy (n = 6 single treatment; n = 2 double treatment) under ultrasound guidance. The goal was to create 2.5-3.0 cm short-axis treatments in similar locations across modalities. Animals were survived for 1 month with contrast-enhanced CT imaging on days 0, 2, 7, 14, and 28. On day 28, necropsy and histopathology were performed. RESULTS: All procedures were well-tolerated. MW ablation zones were longer and more oblong, but equivalent in the short axes to histotripsy zones on immediate post-procedure CT (p < 0.001 and p = 0.45, respectively). Overall, MW volumes were larger (21.4 cm3 vs. 13.4 cm3; p = 0.001) and histotripsy treatment zones were more spherical (p = 0.007). Histotripsy zones were close to the prescribed size (p < 0.001). Over the study period, histotripsy treatment zones decreased in volume while microwave ablation zones slightly increased (-83% vs. +17%, p = 0.001). There were several imaging-only findings: Branch portal vein thrombus with both histotripsy (7/8) and MW (6/6), hematoma in 2/6 MW only, and a gallbladder injury in 1/6 MW animals. The ablation zones demonstrated complete cellular destruction for both modalities. CONCLUSION: Histotripsy was associated with more spherical treatments, fewer biliary complications, and greater treatment zone involution. Hepatic MW and histotripsy treatment in a normal porcine model appear at least equally effective for creating treatment zones with a similar safety profile. KEY POINTS: • Microwave ablation and histotripsy for liver treatment in a healthy porcine model yield equivalent procedural tolerance and cellular destruction. • Histotripsy was associated with more spherical treatments, fewer biliary complications, and greater treatment zone involution over the 28-day follow-up period. • These findings confirm the safety and efficacy of hepatic histotripsy and support the pursuit of clinical trials to further evaluate the translatability of these results.

Reduced SPAG17 Expression in Systemic Sclerosis Triggers Myofibroblast Transition and Drives Fibrosis.

Systemic sclerosis (SSc) is a clinically heterogeneous fibrotic disease with no effective treatment. Myofibroblasts are responsible for unresolving synchronous skin and internal organ fibrosis in SSc, but the drivers of sustained myofibroblast activation remain poorly understood. Using unbiased transcriptome analysis of skin biopsies, we identified the downregulation of SPAG17 in multiple independent cohorts of patients with SSc, and by orthogonal approaches, we observed a significant negative correlation between SPAG17 and fibrotic gene expression. Fibroblasts and endothelial cells explanted from SSc skin biopsies showed reduced chromatin accessibility at the SPAG17 locus. Remarkably, mice lacking Spag17 showed spontaneous skin fibrosis with increased dermal thickness, collagen deposition and stiffness, and altered collagen fiber alignment. Knockdown of SPAG17 in human and mouse fibroblasts and microvascular endothelial cells was accompanied by spontaneous myofibroblast transformation and markedly heightened sensitivity to profibrotic stimuli. These responses were accompanied by constitutive TGF-ß pathway activation. Thus, we discovered impaired expression of SPAG17 in SSc and identified, to our knowledge, a previously unreported cell-intrinsic role for SPAG17 in the negative regulation of fibrotic responses. These findings shed fresh light on the pathogenesis of SSc and may inform the search for innovative therapies for SSc and other fibrotic conditions through SPAG17 signaling.

First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study.

Rationale Current hepatic locoregional therapies are limited in terms of effectiveness and toxicities. Given promising pre-clinical results, a first in-human trial was designed to assess the technical effectiveness and safety profile of histotripsy, a noninvasive, non-thermal, non-ionizing focused ultrasound therapy that creates precise, predictable tissue destruction, in patients with primary and secondary liver tumors.Methods A multicenter phase I trial (Theresa Study) was performed in a single country with 8 weeks of planned follow-up. Eight of fourteen recruited patients were deemed eligible and enrolled in the study. Hepatic histotripsy, was performed with a prototype system (HistoSonics, Inc., Ann Arbor, MI). Eleven tumors were targeted in the 8 patients who all had unresectable end-stage multifocal liver tumors: colorectal liver metastases (CRLM) in 5 patients (7 tumors), breast cancer metastases in 1 (1 tumor), cholangiocarcinoma metastases in 1 (2 tumors), and hepatocellular carcinoma (HCC) in 1 (1 tumor). The primary endpoint was acute technical success, defined as creating a zone of tissue destruction per planned volume assessed by MRI 1-day post-procedure. Safety (device-related adverse events) through 2 months was a secondary endpoint.Results The 8 patients had a median age of 60.4 years with an average targeted tumor diameter of 1.4 cm. The primary endpoint was achieved in all procedures. The secondary safety profile endpoint identified no device-related adverse events. Two patients experienced a continuous decline in tumor markers during the eight weeks following the procedure.Conclusions This first-in-human trial demonstrates that hepatic histotripsy effectively destroys liver tissue in a predictable manner, correlating very well with the planned histotripsy volume, and has a high safety profile without any device-related adverse events. Based on these results, the need for more definitive clinical trials is warranted. Trial Registration: Study to Evaluate VORTX Rx (Theresa). NCT03741088. https://clinicaltrials.gov/ct2/show/NCT03741088 KEY POINTSHistotripsy, a new noninvasive, non-thermal, non-ionizing focused ultrasound therapy, safely created a zone of tissue destruction in the liver that correlated very well with the pre-defined planned tissue destruction volume.In this first human trial histotripsy was well tolerated with no histotripsy device-related adverse events and its primary endpoint of acute technical success was achieved in all 8 enrolled patients with primary or secondary liver tumors.This new locoregional therapy for patients with liver tumors is safe and effective, warranting further trials.

Microwave Ablation as Bridging to Liver Transplant for Patients with Hepatocellular Carcinoma: A Single-Center Retrospective Analysis.

PURPOSE: To evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant. MATERIALS AND METHODS: This retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and who were listed for liver transplantation at a single medical center between 2011 and 2019. The overall survival (OS) rate statuses after liver transplant, waitlist retention, and disease progression were evaluated using the Kaplan-Meier techniques. RESULTS: Among the 88 patients (72 men and 16 women; mean age, 60 years; Model for End-Stage Liver Disease score, 11.2) who were listed for transplant, the median waitlist time was 9.4 months (interquartile range, 5.5-18.9). Seventy-one (80.7%) patients received transplant after a median waitlist time of 8.5 months. Seventeen (19.3%) patients were removed from the waitlist; of these, 4 (4.5%) were removed because of tumors outside of the Milan criteria (HCC-specific dropout). No difference in tumor size or alpha-fetoprotein was observed in the transplanted versus nontransplanted patients at the time of ablation (2.1 vs 2.1 cm and 34.4 vs 34.7 ng/mL for transplanted vs nontransplanted, respectively; P > .05). Five (5.1%) of the 88 patients experienced adverse events after ablation; however, they all recovered. There were no cases of tract seeding. The local tumor progression (LTP) rate was 7.2%. The OS status after liver transplant at 5 years was 76.7%, and the disease-specific survival after LTP was 89.6%, with a median follow-up of 61 months for all patients. CONCLUSIONS: MW ablation appears to be safe and effective for bridging patients with HCC to liver transplant without waitlist removal from seeding, adverse events, or LTP.

Impact of Histotripsy on Development of Intrahepatic Metastases in a Rodent Liver Tumor Model.

Histotripsy has been used for tumor ablation, through controlled, non-invasive acoustic cavitation. This is the first study to evaluate the impact of partial histotripsy ablation on immune infiltration, survival outcomes, and metastasis development, in an in vivo orthotopic, immunocompetent rat HCC model (McA-RH7777). At 7−9 days post-tumor inoculation, the tumor grew to 5−10 mm, and ~50−75% tumor volume was treated by ultrasound-guided histotripsy, by delivering 1−2 cycle histotripsy pulses at 100 Hz PRF (focal peak negative pressure P− >30 MPa), using a custom 1 MHz transducer. Complete local tumor regression was observed on MRI in 9/11 histotripsy-treated rats, with no local recurrence or metastasis up to the 12-week study end point, and only a <1 mm residual scar tissue observed on histology. In comparison, 100% of untreated control animals demonstrated local tumor progression, developed intrahepatic metastases, and were euthanized at 1−3 weeks. Survival outcomes in histotripsy-treated animals were significantly improved compared to controls (p-value < 0.0001). There was evidence of potentially epithelial-to-mesenchymal transition (EMT) in control tumor and tissue healing in histotripsy-treated tumors. At 2- and 7-days post-histotripsy, increased immune infiltration of CD11b+, CD8+ and NK cells was observed, as compared to controls, which may have contributed to the eventual regression of the untargeted tumor region in histotripsy-treated tumors.