Interpreting the complexities of the plastid genome in dinoflagellates: a mini-review of recent advances.

Photosynthetic dinoflagellates play crucial roles in global primary production and carbon fixation. Despite their success in filling various ecological niches, numerous mysteries about their plastid evolution and plastid genomes remain unsolved. The plastid genome of dinoflagellates presents one of the most complex lineages in the biological realm, mainly due to multiple endosymbiotic plastid events in their evolutionary history. Peridinin-containing dinoflagellates possess the most reduced and fragmented genome, with only a few genes located on multiple "minicircles", whereas replacement plastids in dinoflagellate lineages have undergone different degrees of endosymbiotic gene transfer. Recent advancements in high-throughput sequencing have improved our understanding of plastid genomes and plastid-encoded gene expression in many dinoflagellate species. Plastid transcripts of dinoflagellates exhibit two unconventional processing pathways: the addition of a 3' poly(U) tail and substitutional RNA editing. These pathways are widely employed across dinoflagellate lineages, which are possibly retained from the ancestral peridinin plastid. This mini-review summarizes the developments in the plastid genomes of dinoflagellates and pinpoints the research areas that necessitate further exploration, aiming to provide valuable insights into plastid evolution in these fascinating and important organisms.

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.

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.

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.

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.

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.

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.

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.

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..

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.

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.

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.

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.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

CT Fluoroscopy for Image-Guided Procedures: Physician Radiation Dose During Full-Rotation and Partial-Angle CT Scanning.

PURPOSE: To determine physician radiation exposure when using partial-angle computed tomography (CT) fluoroscopy (PACT) vs conventional full-rotation CT and whether there is an optimal tube/detector position at which physician dose is minimized. MATERIALS AND METHODS: Physician radiation dose (entrance air kerma) was measured for full-rotation CT (360°) and PACT (240°) at all tube/detector positions using a human-mimicking phantom placed in a 64-channel multidetector CT. Parameters included 120 kV, 20- and 40-mm collimation, and 100 mA. The mean, standard deviation, and increase/decrease in physician dose compared with a full-rotation scan were reported. RESULTS: Physician radiation exposure during CT fluoroscopy with PACT was highly dependent on the position of the tube/detector during scanning. The lowest PACT physician dose was when the physician was on the detector side (center view angle 116°; -35% decreased dose vs full-angle CT). The highest PACT physician dose was with the physician on the tube side (center view angle 298°; +34% increased dose vs full-angle CT), all doses P <.05 vs full-rotation CT. CONCLUSIONS: Partial-angle CT has the potential to both significantly increase or decrease physician radiation dose during CT fluoroscopy-guided procedures. The detector/tube position has a profound effect on physician dose. The lowest dose during PACT was achieved when the physician was located on the detector side (ie, distant from the tube). This data could be used to optimize CT fluoroscopy parameters to reduce physician radiation exposure for PACT-capable scanners.

Percutaneous Lung Biopsy with Pleural and Parenchymal Blood Patching: Results and Complications from 1,112 Core Biopsies.

PURPOSE: To evaluate the outcomes of computed tomography (CT) fluoroscopy-guided core lung biopsies with emphasis on diagnostic yield, complications, and efficacy of parenchymal and pleural blood patching to avoid chest tube placement. METHODS: This is a single-center retrospective analysis of CT fluoroscopy-guided percutaneous core lung biopsies between 2006 and 2020. Parenchymal blood patching during introducer needle withdrawal was performed in 74% of cases as a preventive measure, and pleural blood patching was the primary salvage maneuver for symptomatic or growing pneumothorax in 60 of 83 (72.2%) applicable cases. RESULTS: A total of 1,029 patients underwent 1,112 biopsies (532 men; mean age, 66 years; 38.6%, history of emphysema; lesion size, 16.7 mm). The diagnostic yield was 93.6% (1,032/1,103). Fewer complications requiring intervention were observed in patients who underwent parenchymal blood patching (5.7% vs 14.2%, P < .001). Further intervention was required in 83 of 182 pneumothorax cases, which included the following: (a) pleural blood patch (5.4%, 60/1,112), (b) chest tube placement without a pleural blood patch attempt (1.5%, 17/1,112), and (c) simple aspiration (0.5%, 6/1,112). Pleural blood patch as monotherapy was successful in 83.3% (50/60) of cases without need for further intervention. The overall chest tube rate was 2.6% (29/1,112). Emphysema was the only significant risk factor for complications requiring intervention (P ≤ .001). CONCLUSIONS: Parenchymal blood patching during introducer needle withdrawal decreased complications requiring intervention. Salvage pleural blood patching reduced the frequency of chest tube placement for pneumothorax.

Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound.

Histotripsy is the first noninvasive, non-ionizing, and non-thermal ablation technology guided by real-time imaging. Using focused ultrasound delivered from outside the body, histotripsy mechanically destroys tissue through cavitation, rendering the target into acellular debris. The material in the histotripsy ablation zone is absorbed by the body within 1-2 months, leaving a minimal remnant scar. Histotripsy has also been shown to stimulate an immune response and induce abscopal effects in animal models, which may have positive implications for future cancer treatment. Histotripsy has been investigated for a wide range of applications in preclinical studies, including the treatment of cancer, neurological diseases, and cardiovascular diseases. Three human clinical trials have been undertaken using histotripsy for the treatment of benign prostatic hyperplasia, liver cancer, and calcified valve stenosis. This review provides a comprehensive overview of histotripsy covering the origin, mechanism, bioeffects, parameters, instruments, and the latest results on preclinical and human studies.

Noninvasive thyroid histotripsy treatment: proof of concept study in a porcine model.

INTRODUCTION: This study was performed to determine the feasibility and safety of creating superficial histotripsy treatment in a live porcine thyroid model. METHODS: The porcine thymus comparable in size, shape and location to the human thyroid was used for this study. This model has been used for thyroid surgery studies due to the diminutive size of the porcine thyroid. Four female swine underwent a total of eight histotripsy treatments performed with a prototype therapy system (HistoSonics, Inc., Ann Arbor, MI). Two treatments were performed in each animal: a spherical 1.0 × 1.0 × 1.0 cm and ovoid 1.0 × 1.0 × 2.0 cm treatment zones. MRI immediately post-procedure was evaluated for histotripsy treatment zone size and imaging appearance, followed immediately by sacrifice. Tissue was then reviewed for percent cellular destruction and precision. RESULTS: Treatment zones measured on post treatment MRI were similar to prescribed volumes (spherical = 0.60 (+/- 0.11) cm3, ovoid = 1.23 (+/- 0.40) cm3, p > 0.05 vs. prescribed). MRI demonstrated well demarcated treatment zones and imaging findings consistent with cellular destruction. Histology demonstrated sharp transitions to normal tissue (mean 0.33 (+/- 0.13) cm), and high degrees of cellular destruction (mean 76% (+/- 12.5), range of 50-100%) in the treated tissue. Edema within the overlying muscle was seen in 2/8 treatments. CONCLUSION: Histotripsy is capable of safely creating precise histotripsy treatments within the superficial neck of a porcine thyroid model without evidence of considerable complications.

Proteome Analysis of Whole-Body Responses in Medaka Experimentally Exposed to Fish-Killing Dinoflagellate Karenia mikimotoi.

Karenia mikimotoi is a well-known harmful algal bloom species. Blooms of this dinoflagellate have become a serious threat to marine life, including fish, shellfish, and zooplanktons and are usually associated with massive fish death. Despite the discovery of several toxins such as gymnocins and gymnodimines in K. mikimotoi, the mechanisms underlying the ichthyotoxicity of this species remain unclear, and molecular studies on this topic have never been reported. The present study investigates the fish-killing mechanisms of K. mikimotoi through comparative proteomic analysis. Marine medaka, a model fish organism, was exposed to K. mikimotoi for a three-part time period (LT25, LT50 and LT90). Proteins extracted from the whole fish were separated by using two-dimensional gel electrophoresis, and differentially expressed proteins were identified with reference to an untreated control. The change in fish proteomes over the time-course of exposure were analyzed. A total of 35 differential protein spots covering 19 different proteins were identified, of which most began to show significant change in expression levels at the earliest stage of intoxication. Among the 19 identified proteins, some are closely related to the oxidative stress responses, energy metabolism, and muscle contraction. We propose that oxidative stress-mediated muscle damage might explain the symptoms developed during the ichthyotoxicity test, such as gasping for breath, loss of balance, and body twitching. Our findings lay the foundations for more in-depth studies of the mechanisms of K. mikimotoi's ichthyotoxicity.