Current state of implementation of in silico tools in the biopharmaceutical industry-Proceedings of the 5th modeling workshop.

The fifth modeling workshop (5MW) was held in June 2023 at Favrholm, Denmark and sponsored by Recovery of Biological Products Conference Series. The goal of the workshop was to assemble modeling practitioners to review and discuss the current state, progress since the last fourth mini modeling workshop (4MMW), gaps and opportunities for development, deployment and maintenance of models in bioprocess applications. Areas of focus were four categories: biophysics and molecular modeling, mechanistic modeling, computational fluid dynamics (CFD) and plant modeling. Highlights of the workshop included significant advancements in biophysical/molecular modeling to novel protein constructs, mechanistic models for filtration and initial forays into modeling of multiphase systems using CFD for a bioreactor and mapped strategically to cell line selection/facility fit. A significant impediment to more fully quantitative and calibrated models for biophysics is the lack of large, anonymized datasets. A potential solution would be the use of specific descriptors in a database that would allow for detailed analyzes without sharing proprietary information. Another gap identified was the lack of a consistent framework for use of models that are included or support a regulatory filing beyond the high-level guidance in ICH Q8-Q11. One perspective is that modeling can be viewed as a component or precursor of machine learning (ML) and artificial intelligence (AI). Another outcome was alignment on a key definition for "mechanistic modeling." Feedback from participants was that there was progression in all of the fields of modeling within scope of the conference. Some areas (e.g., biophysics and molecular modeling) have opportunities for significant research investment to realize full impact. However, the need for ongoing research and development for all model types does not preclude the application to support process development, manufacturing and use in regulatory filings. Analogous to ML and AI, given the current state of the four modeling types, a prospective investment in educating inter-disciplinary subject matter experts (e.g., data science, chromatography) is essential to advancing the modeling community.

Contrast-enhanced US Evaluation of Hepatocellular Carcinoma Response to Chemoembolization: A Prospective Multicenter Trial.

Background Contrast-enhanced (CE) US has been studied for use in the detection of residual viable hepatocellular carcinoma (HCC) after locoregional therapy, but multicenter data are lacking. Purpose To compare two-dimensional (2D) and three-dimensional (3D) CE US diagnostic performance with that of CE MRI or CT, the current clinical standard, in the detection of residual viable HCC after transarterial chemoembolization (TACE) in a prospective multicenter trial. Materials and Methods Participants aged at least 21 years with US-visible HCC scheduled for TACE were consecutively enrolled at one of three participating academic medical centers from May 2016 to March 2022. Each underwent baseline 2D and 3D CE US before TACE, 2D and 3D CE US 1-2 weeks and/or 4-6 weeks after TACE, and CE MRI or CT 4-6 weeks after TACE. CE US and CE MRI or CT were evaluated by three fellowship-trained radiologists for the presence or absence of viable tumors and were compared with reference standards of pathology (18%), angiography on re-treatment after identification of residual disease at 1-2-month follow-up imaging (31%), 4-8-month CE MRI or CT (42%), or short-term (approximately 1-2 months) CE MRI or CT if clinically decompensated and estimated viability was greater than 50% at imaging (9%). Diagnostic performance criteria, including sensitivity and specificity, were obtained for each modality and time point with generalized estimating equation analysis. Results A total of 132 participants were included (mean age, 64 years ± 7 [SD], 87 male). Sensitivity of 2D CE US 4-6 weeks after TACE was 91% (95% CI: 84, 95), which was higher than that of CE MRI or CT (68%; 95% CI: 58, 76; P < .001). Sensitivity of 3D CE US 4-6 weeks after TACE was 89% (95% CI: 81, 94), which was higher than that of CE MRI or CT (P < .001), with no evidence of a difference from 2D CE US (P = .22). CE MRI or CT had 85% (95% CI: 76, 91) specificity, higher than that of 4-6-week 2D and 3D CE US (70% [95% CI: 56, 80] and 67% [95% CI: 53, 78], respectively; P = .046 and P = .023, respectively). No evidence of differences in any diagnostic criteria were observed between 1-2-week and 4-6-week 2D CE US (P > .21). Conclusion The 2D and 3D CE US examinations 4-6 weeks after TACE revealed higher sensitivity in the detection of residual HCC than CE MRI or CT, albeit with lower specificity. Importantly, CE US performance was independent of follow-up time. Clinical trial registration no. NCT02764801 © RSNA, 2023 Supplemental material is available for this article.

Outcomes of Transarterial Embolization for Acute Nonvariceal Upper Gastrointestinal Bleeding: Correlation with Periprocedural Endoscopy.

PURPOSE: To evaluate gastric and intestinal mucosal changes on postembolic endoscopy and mortality after transarterial embolization (TAE) for upper gastrointestinal bleeding (UGIB). MATERIALS AND METHODS: An institutional review board-approved retrospective review of patients who underwent arteriography for refractory UGIB at a multicenter health system from December 2003 to August 2019 was performed. Two hundred sixty-nine patients underwent TAE for UGIB. Data on etiology of bleeding, embolization technique, pre-embolic and postembolic endoscopic results, blood product requirements, and mortality were collected from the medical record. Endoscopy results were compared at the site of the target lesion before and after TAE. Multivariable logistic regressions were performed to assess predictors of new adverse mucosal responses and mortality. RESULTS: The most common etiology of UGIB was peptic ulcer. Twenty-five percent (n = 68) of the patients had clinical evidence of rebleeding after TAE, and the 30-day mortality rate was 26% (n = 73). Eighty-eight (32%) patients underwent post-TAE endoscopy, with only 15% showing new adverse mucosal changes after embolization. Procedural characteristics, including vascular territory and embolic choice, were not significantly predictive of increased risk of development of adverse mucosal response after TAE or increased mortality risk. No patients in the study were found to have bowel lumen stenosis at the time of post-TAE endoscopy or at 6 year follow-up. CONCLUSIONS: TAE is a safe and effective intervention for patients with UGIB. Post-TAE endoscopy demonstrated that most patients had either stability or improvement in the target lesion after TAE, and only a minority of patients demonstrated adverse mucosal changes.

New Developments in Image-Guided Percutaneous Irreversible Electroporation of Solid Tumors.

PURPOSE OF REVIEW: This review will describe the various applications, benefits, risks, and approaches of conventional irreversible electroporation (IRE), as well as highlight the new technological developments of this procedure along with their clinical applications. RECENT FINDINGS: Minimally invasive image-guided percutaneous IRE ablation has emerged as a newer, non-thermal ablation technique for tumors in the solid organs, particularly within the liver, pancreas, kidney, and prostate. IRE allows for ablation near heat-sensitive structures, including major blood vessels and nerves, and is not susceptible to the heat sink effect. However, it is limited by certain requirements, such as the need for precise parallel placement of at least two probes with a maximum inter-probe distance of 2.5 cm to reduce the risk of arching phenomenon, the requirement for general anesthesia with muscle relaxant, and the need for cardiac synchronization. However, new technological advancements in the ablation system and image guidance tools have been introduced to improve the efficiency and efficacy of IRE. IRE is a safe and effective treatment option for solid tumor ablation within the liver, pancreas, kidney, and prostate. Compared with other ablation techniques, IRE has several advantages, such as the absence of heat sink effect and minimal injury to blood vessels and bile ducts while activating the immune system. Novel techniques such as H-FIRE, needle placement systems, and robotics have enhanced the accuracy and performance in placement of IRE probes. IRE can be especially beneficial when combined with chemotherapy, immunomodulation, and immunotherapy.

Transarterial Embolization Modulates the Immune Response within Target and Nontarget Hepatocellular Carcinomas in a Rat Model.

Background Transarterial embolization (TAE) is the most common treatment for hepatocellular carcinoma (HCC); however, there remain limited data describing the influence of TAE on the tumor immune microenvironment. Purpose To characterize TAE-induced modulation of the tumor immune microenvironment in a rat model of HCC and identify factors that modulate this response. Materials and Methods TAE was performed on autochthonous HCCs induced in rats with use of diethylnitrosamine. CD3, CD4, CD8, and FOXP3 lymphocytes, as well as programmed cell death protein ligand-1 (PD-L1) expression, were examined in three cohorts: tumors from rats that did not undergo embolization (control), embolized tumors (target), and nonembolized tumors from rats that had a different target tumor embolized (nontarget). Differences in immune cell recruitment associated with embolic agent type (tris-acryl gelatin microspheres [TAGM] vs hydrogel embolics) and vascular location were examined in rat and human tissues. A generalized estimating equation model and t, Mann-Whitney U, and χ2 tests were used to compare groups. Results Cirrhosis-induced alterations in CD8, CD4, and CD25/CD4 lymphocytes were partially normalized following TAE (CD8: 38.4%, CD4: 57.6%, and CD25/CD4: 21.1% in embolized liver vs 47.7% [P = .02], 47.0% [P = .01], and 34.9% [P = .03], respectively, in cirrhotic liver [36.1%, 59.6%, and 4.6% in normal liver]). Embolized tumors had a greater number of CD3, CD4, and CD8 tumor-infiltrating lymphocytes relative to controls (191.4 cells/mm2 vs 106.7 cells/mm2 [P = .03]; 127.8 cells/mm2 vs 53.8 cells/mm2 [P < .001]; and 131.4 cells/mm2 vs 78.3 cells/mm2 [P = .01]) as well as a higher PD-L1 expression score (4.1 au vs 1.9 au [P < .001]). A greater number of CD3, CD4, and CD8 lymphocytes were found near TAGM versus hydrogel embolics (4.1 vs 2.0 [P = .003]; 3.7 vs 2.0 [P = .01]; and 2.2 vs 1.1 [P = .03], respectively). The number of lymphocytes adjacent to embolics differed based on vascular location (17.9 extravascular CD68+ peri-TAGM cells vs 7.0 intravascular [P < .001]; 6.4 extravascular CD68+ peri-hydrogel embolic cells vs 3.4 intravascular [P < .001]). Conclusion Transarterial embolization-induced dynamic alterations of the tumor immune microenvironment are influenced by underlying liver disease, embolic agent type, and vascular location. © RSNA, 2022 Online supplemental material is available for this article. See also the editorials by Kennedy et al and by White in this issue.

Preintervention Computed Tomography Improves the Performance of Endovascular Intervention in Patients with Abdominopelvic Trauma.

PURPOSE: To evaluate the role of computed tomography (CT) and CT angiography in guiding endovascular arteriography (EA) and embolization in hemodynamically (HD) stable and unstable patients with abdominal and/or pelvic (AP) trauma. MATERIALS AND METHODS: A retrospective review was performed of patients with AP trauma who underwent EA with or without embolization (from January 2012 to August 2020) at an urban, level I trauma center. Patients aged <18 years or those undergoing EA outside of the abdomen and/or pelvis were excluded. Demographics, imaging findings, procedure length, contrast agent administration, laboratory values, and outcomes were compared on the basis of preprocedural imaging technique and hemodynamic status. RESULTS: A total of 190 patients with AP trauma underwent EA with or without embolization; among them, 123 were HD stable and underwent CT/CT angiography, whereas 67 were initially HD unstable and underwent operative management prior to EA. Of these patients, 38 underwent CT/CT angiography after hemodynamic stability was achieved prior to postoperative EA. The incidence of therapeutic embolization for arterial injury on EA was significantly higher in patients with preprocedural CT/CT angiography (65.8% vs 44.8%, P = .04). The positive and negative predictive values of CT angiography for arterial injury at the time of EA were 92.3% and 100%, respectively. Prior imaging was associated with a reduced contrast agent requirement at the time of EA and reduced transfusion requirement (P = .05 and P = .02). No significant differences were observed in adverse outcomes for patients undergoing preprocedural imaging. CONCLUSIONS: CT or CT angiography prior to EA for HD stable and unstable patients with AP trauma may improve the likelihood of therapeutic embolization and enable improved procedure metrics without increasing adverse outcomes.

Molecular imaging in management of colorectal metastases by the interventional oncologist.

Interventional oncologists provide several effective treatment options for patients with metastatic colorectal cancer (mCRC), including embolization and ablation-based techniques. Molecular imaging methods such as positron emission tomography (PET) can play an important role in managing mCRC patients. In this review, we aim to highlight the role of molecular imaging in mCRC management by interventional oncologists including: initial staging and pretreatment planning; predicting molecular subtypes, prognosis, and treatment outcomes; intraprocedural guidance; and assessing treatment response and post-procedural monitoring.

Multicenter assessment of augmented reality registration methods for image-guided interventions.

PURPOSE: To evaluate manual and automatic registration times and registration accuracies on HoloLens 2 for aligning a 3D CT phantom model onto a CT grid, a crucial step for intuitive 3D navigation during CT-guided interventions; to compare registration times between HoloLens 1 and 2. METHODS: Eighteen participants in various stages of clinical training across two academic centers performed registration of a 3D CT phantom model onto a CT grid using HoloLens 2. Registration times and accuracies were compared among different registration methods, clinical experience levels, and consecutive attempts. Registration times were also compared retrospectively to prior HoloLens 1 results. RESULTS: Mean aggregate manual registration times were 27.7 s, 24.3 s, and 72.8 s for one-handed gesture, two-handed gesture, and Xbox controller, respectively; mean automatic registration time was 5.3 s (ANOVA p < 0.0001). No significant difference in registration times was found among attendings, residents and fellows, and medical students (p > 0.05). Significant improvements in registration times were detected across consecutive attempts using hand gestures (p < 0.01). Compared to prior HoloLens 1 data, hand gesture registration was 81.7% faster with HoloLens 2 (p < 0.05). Registration accuracies were not significantly different across manual registration methods, measuring at 5.9 mm, 9.5 mm, and 8.6 mm with one-handed gesture, two-handed gesture, and Xbox controller, respectively (p > 0.05). CONCLUSIONS: Manual registration times decreased significantly on HoloLens 2, approaching those of automatic registration and outperforming Xbox controller registration. Fast, adaptive, and accurate registration of holographic models of cross-sectional imaging is paramount for the implementation of augmented reality-assisted 3D navigation during CT-guided interventions.

Neurology and the histiocytoses: a case of Rosai-Dorfman-Destombes disease.

The histiocytoses are a group of rare disorders characterised by the accumulation of neoplastic or non-neoplastic activated histiocytes in various tissues. Phenotypes vary widely from cutaneous lesions or lymphadenopathy that regress spontaneously to disseminated disease with poor prognosis. Neurological symptoms can be a presenting feature or appear during the course of disease. We present a challenging diagnostic and management case of Rosai-Dorfman-Destombes disease in a 48-year-old woman with a relapsing, partially steroid-responsive syndrome comprising patchy, non-length-dependent radiculoneuropathy with diffuse pachymeningitis and widespread systemic disease, and recent dramatic response to novel mitogen-activated kinase pathway inhibition. We discuss the clinical characteristics, diagnosis, recent breakthroughs in pathogenesis and emerging treatment options for Rosai-Dorfman disease and for the histiocytoses with neurological sequelae, including Langerhans cell histiocytosis and Erdheim-Chester disease.

Hyperpolarized Metabolic Imaging Detects Latent Hepatocellular Carcinoma Domains Surviving Locoregional Therapy.

BACKGROUND AND AIMS: Advances in cancer treatment have improved survival; however, local recurrence and metastatic disease-the principal causes of cancer mortality-have limited the ability to achieve durable remissions. Local recurrences arise from latent tumor cells that survive therapy and are often not detectable by conventional clinical imaging techniques. Local recurrence after transarterial embolization (TAE) of hepatocellular carcinoma (HCC) provides a compelling clinical correlate of this phenomenon. In response to TAE-induced ischemia, HCC cells adapt their growth program to effect a latent phenotype that precedes local recurrence. APPROACH AND RESULTS: In this study, we characterized and leveraged the metabolic reprogramming demonstrated by latent HCC cells in response to TAE-induced ischemia to enable their detection in vivo using dynamic nuclear polarization (DNP) magnetic resonance spectroscopic imaging (MRSI) of 13 carbon-labeled substrates. Under TAE-induced ischemia, latent HCC cells demonstrated reduced metabolism and developed a dependence on glycolytic flux to lactate. Despite the hypometabolic state of these cells, DNP-MRSI of 1-13 C-pyruvate and its downstream metabolites, 1-13 C-lactate and 1-13 C-alanine, predicted histological viability. CONCLUSIONS: These studies provide a paradigm for imaging latent, treatment-refractory cancer cells, suggesting that DNP-MRSI provides a technology for this application.

Infection Rates Following Hepatic Embolotherapy in Patients with Prior Biliary Interventions: Comparison of Single-Drug Moxifloxacin and Multidrug Antibiotic Prophylaxis.

PURPOSE: To investigate the incidence of infection in patients with prior biliary interventions undergoing hepatic embolotherapy following extended antibiotic prophylaxis using moxifloxacin monotherapy or a multidrug regimen. MATERIAL AND METHODS: Under an Institutional Review Board-approved protocol, retrospective review of a quality assurance database identified all liver-directed therapies (LDTs) at a tertiary care center between 2010 and 2019 with biliary intervention prior to LDT Records were reviewed for infectious complications within 3 months of chemo- or radioembolization. Patients were categorized based on extended antibiotic prophylaxis regimen: oral moxifloxacin monotherapy or multidrug regimen of levofloxacin and metroniodazole plus preprocedural neomycin and erythromycin. Procedures without at least 2 months of clinical follow-up, hepatic ablation, and procedures without extended antibiotic prophylaxis were excluded Regression analysis was used to analyze multivariate data to detect a difference in infection rate. RESULTS: Twenty-four chemoembolization and 58 radioembolization procedures were performed on 55 patients with prior biliary interventions. Forty-four used monotherapy and 38 used multidrug regimen. The incidence of infection was 16.7% (4/24) after chemoembolization and 13.8% (8/58) after radioembolization The incidence of infection in patients did not differ between antibiotic prophylaxis regimens (18.2% [8/44] with moxifloxacin monotherapy and 10.5% [4/38] multidrug regimen, P = .3) or between types of biliary interventions (24.1% [7/29] with bilioenteric anastomosis and 23.8% [5/21] biliary stenting, P = .3). CONCLUSIONS: The types of extended antibiotic prophylaxis (moxifloxacin monotherapy vs multitherapy), prior biliary intervention, and embolotherapy were not found to be associated with differences in the incidence of infectious complications in this population.

Editorial Commentary: Hip Cam Overresection May Result in Inferior Outcomes: The Goldilocks Paradox of Too Little, Too Much, or Just Right?

Femoroacetabular impingement is a recognized source of hip pain and cause of labral and articular cartilage injury. Persistent femoroacetabular impingement has been recognized as a source of inferior patient-reported outcomes, and attempts to define a "normal" α-angle has resulted in more aggressive resection of cam lesions. An overzealous femoroplasty may result in iatrogenic hip instability. A dynamic intraoperative examination may be the best way to truly recognize this problem, in particular, by visualizing the loss of the suction seal, as the cam resection engages the acetabulum, resulting in subluxation. A soft tissue "remplissage" salvage procedure may offer an option to correct cam overresection and improve patient outcomes during revision arthroscopy, as we continue to search for the "right" amount of cam correction to perform.

Toward in silico CMC: An industrial collaborative approach to model-based process development.

The Third Modeling Workshop focusing on bioprocess modeling was held in Kenilworth, NJ in May 2019. A summary of these Workshop proceedings is captured in this manuscript. Modeling is an active area of research within the biotechnology community, and there is a critical need to assess the current state and opportunities for continued investment to realize the full potential of models, including resource and time savings. Beyond individual presentations and topics of novel interest, a substantial portion of the Workshop was devoted toward group discussions of current states and future directions in modeling fields. All scales of modeling, from biophysical models at the molecular level and up through large scale facility and plant modeling, were considered in these discussions and are summarized in the manuscript. Model life cycle management from model development to implementation and sustainment are also considered for different stages of clinical development and commercial production. The manuscript provides a comprehensive overview of bioprocess modeling while suggesting an ideal future state with standardized approaches aligned across the industry.

Augmented and Mixed Reality: Technologies for Enhancing the Future of IR.

Augmented and mixed reality are emerging interactive and display technologies. These technologies are able to merge virtual objects, in either 2 or 3 dimensions, with the real world. Image guidance is the cornerstone of interventional radiology. With augmented or mixed reality, medical imaging can be more readily accessible or displayed in actual 3-dimensional space during procedures to enhance guidance, at times when this information is most needed. In this review, the current state of these technologies is addressed followed by a fundamental overview of their inner workings and challenges with 3-dimensional visualization. Finally, current and potential future applications in interventional radiology are highlighted.

Three-Dimensional Augmented Reality Visualization Informs Locoregional Therapy in a Translational Model of Hepatocellular Carcinoma.

PURPOSE: To evaluate the utility of visualizing preprocedural MR images in 3-dimensional (3D) space using augmented reality (AR) before transarterial embolization of hepatocellular carcinoma (HCC) in a preclinical model. MATERIALS AND METHODS: A total of 28 rats with diethylnitrosamine-induced HCCs > 5 mm treated with embolization were included in a prospective study. In 12 rats, 3D AR visualization of preprocedural MR images was performed before embolization. Procedural metrics including catheterization time and radiation exposure were compared vs a prospective cohort of 16 rats in which embolization was performed without AR. An additional cohort of 15 retrospective cases was identified and combined with the prospective control cohort (n = 31) to improve statistical power. RESULTS: A 37% reduction in fluoroscopy time, from 11.7 min to 7.4 minutes, was observed with AR when compared prospectively, which did not reach statistical significance (P = .12); however, when compared with combined prospective and retrospective controls, the reduction in fluoroscopy time from 14.1 min to 7.4 minutes (48%) was significant (P = .01). A 27% reduction in total catheterization time, from 42.7 minutes to 31.0 minutes, was also observed with AR when compared prospectively, which did not reach statistical significance (P = .11). No significant differences were seen in dose-area product or air kerma prospectively. CONCLUSIONS: Three-dimensional AR visualization of preprocedural imaging may aid in the reduction of procedural metrics in a preclinical model of transarterial embolization. These data support the need for further studies to evaluate the potential of AR in endovascular oncologic interventions.

MR Imaging Enables Real-Time Monitoring of In Vitro Electrolytic Ablation of Hepatocellular Carcinoma.

PURPOSE: To evaluate the capability of T2-weighted magnetic resonance (MR) imaging to monitor electrolytic ablation-induced cell death in real time. MATERIALS AND METHODS: Agarose phantoms arranged as an electrolytic cell were exposed to varying quantities of electric charge under constant current to create a pH series. The pH phantoms were subjected to T2-weighted imaging with region of interest quantitation of the acquired signal intensity. Subsequently, hepatocellular carcinoma (HCC) cells encapsulated in an agarose gel matrix were subjected to 10 V of electrolytic ablation for variable lengths of time with and without concurrent T2-weighted MR imaging. Cellular death was confirmed by a fluorescent reporter. Finally, to confirm that real-time MR images corresponded to ablation zones, 10 V electrolytic ablations were performed followed by the addition of pH-neutralizing 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer. RESULTS: Analysis of MR imaging from agarose gel pH phantoms demonstrated a relationship between signal intensity and pH at the anodes and cathodes. The steep negative phase of the anode model (pH < 3.55) and global minimum of the cathode model (pH ≈ 11.62) closely approximated established cytotoxic pH levels. T2-weighted MR imaging demonstrated a strong correlation of ablation zones with regions of HCC cell death (r = 0.986; R2 = 0.916; P < .0001). The addition of HEPES buffer to the hydrogel resulted in complete obliteration of MR imaging-observed ablation zones, confirming that change in pH directly caused the observed signal intensity attenuation of the ablation zone. CONCLUSIONS: T2-weighted MR imaging enabled the real-time detection of electrolytic ablation zones, demonstrating a strong correlation with histologic cell death.

Editorial Commentary: "Loose Lips Sink Ships"-But What About "Loose Hips"?

Hip instability continues to be a challenge in hip preservation. Our understanding of the role of osseous anatomy, labral integrity and soft-tissue stabilizers has increased dramatically over the past several decades. Connective-tissue disorders such as Ehlers-Danlos syndrome pose a significant challenge to the management of instability in all joints but particularly in the hip. Ligamentum teres tears have been found to be more common than previously thought, although their significance is still not well understood. In patients with both Ehlers-Danlos syndrome and ligamentum teres tears, reconstruction and capsular plication result in moderate success, but not in all cases.

Immunotherapy and the Interventional Oncologist: Challenges and Opportunities-A Society of Interventional Oncology White Paper.

Interventional oncology is a subspecialty field of interventional radiology that addresses the diagnosis and treatment of cancer and cancer-related problems by using targeted minimally invasive procedures performed with image guidance. Immuno-oncology is an innovative area of cancer research and practice that seeks to help the patient's own immune system fight cancer. Both interventional oncology and immuno-oncology can potentially play a pivotal role in cancer management plans when used alongside medical, surgical, and radiation oncology in the care of cancer patients.

Angiographic Atlas of the Visceral Vascular Anatomy in Translational Rat Models.

PURPOSE: To characterize angiographic and cross-sectional imaging anatomy of the rat visceral vasculature in 2 translational models. MATERIALS AND METHODS: Animal studies were conducted in accordance with institutional guidelines and approval of the Institutional Animal Care and Use Committees. Retrospective review of digital subtraction arteriography was performed in 65 Wistar and 50 Sprague-Dawley male rats through a left common carotid artery or right common femoral artery approach. MR imaging of the abdomen was performed on the rats to correlate imaging modalities. RESULTS: Aortography was performed in 3 locations, including cranial to the celiac artery, cranial to the renal arteries, and cranial to the caudal (inferior) mesenteric artery, enabling characterization of the visceral branch arteries in all 65 Wistar rats. Selective arteriography of first-, second-, and third-order branch vessels of the aorta was performed allowing characterization of normal and variant anatomy. Dedicated selective arteriography was performed of the celiac artery in 65 Wistar and 10 Sprague-Dawley rats, of the common hepatic artery in 65 Wistar and 50 Sprague-Dawley rats, and of the cranial mesenteric artery in 43 Wistar rats. MR imaging enabled correlation with the lobar and portal venous anatomy. CONCLUSIONS: Analysis of arteriography and MR imaging in these rat models will provide translational researchers with anatomic details needed to develop new endovascular protocols for small animal research in interventional radiology.

Association of Complete Radiologic and Pathologic Response following Locoregional Therapy before Liver Transplantation with Long-Term Outcomes of Hepatocellular Carcinoma: A Retrospective Study.

PURPOSE: To evaluate long-term outcomes of patients with hepatocellular carcinoma (HCC) who show a complete response (CR) vs non-CR on pretransplantation imaging studies or pathologic evaluation of liver explants after locoregional therapy (LRT) before liver transplantation. MATERIALS AND METHODS: Patients listed for liver transplantation for HCC (March 1998 to December 2010) undergoing LRT with available multiphase MR/CT imaging before transplantation were included. Pathologic response was evaluated based on liver explant pathology. A total of 108 patients (17 women; 16%) met the inclusion criteria. RESULTS: Radiologic CR was achieved in 65 patients (60%) vs non-CR in 43 (40%), and pathologic CR was achieved in 36 patients (33%) vs non-CR in 72 (67%). Mean 5-year overall survival (OS) from the time of listing and recurrence-free survival (RFS) after liver transplantation were significantly better for patients with pathologic CR vs non-CR on explant pathology (OS, 83.3% vs 65.2% [28% difference; P = .046]; RFS, 80.6% vs 62.5% [29% difference; P = .045]). Mean 5-y OS and RFS were not significantly different between patients with radiologic CR or non-CR on pretransplantation imaging (OS, 75.4% vs 65.1% [P = .12]; RFS, 74% vs 62.8% [P = .17]). CONCLUSIONS: Achievement of a pathologic CR vs non-CR in response to LRT before liver transplantation for HCC is associated with improved OS from time of listing and improved RFS after liver transplantation. However, current imaging paradigms fall short of accurate delineation of response to LRT, resulting in poor correlation of outcomes between pathologic and radiologic CR.