Comprehensive Assessment of Coronary Artery Disease by Using First-Pass Analysis Dynamic CT Perfusion: Validation in a Swine Model.

Purpose To retrospectively validate a first-pass analysis (FPA) technique that combines computed tomographic (CT) angiography and dynamic CT perfusion measurement into one low-dose examination. Materials and Methods The study was approved by the animal care committee. The FPA technique was retrospectively validated in six swine (mean weight, 37.3 kg ± 7.5 [standard deviation]) between April 2015 and October 2016. Four to five intermediate-severity stenoses were generated in the left anterior descending artery (LAD), and 20 contrast material-enhanced volume scans were acquired per stenosis. All volume scans were used for maximum slope model (MSM) perfusion measurement, but only two volume scans were used for FPA perfusion measurement. Perfusion measurements in the LAD, left circumflex artery (LCx), right coronary artery, and all three coronary arteries combined were compared with microsphere perfusion measurements by using regression, root-mean-square error, root-mean-square deviation, Lin concordance correlation, and diagnostic outcomes analysis. The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were also determined. Results FPA and MSM perfusion measurements (PFPA and PMSM) in all three coronary arteries combined were related to reference standard microsphere perfusion measurements (PMICRO), as follows: PFPA_COMBINED = 1.02 PMICRO_COMBINED + 0.11 (r = 0.96) and PMSM_COMBINED = 0.28 PMICRO_COMBINED + 0.23 (r = 0.89). The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were 10.8 and 17.8 mGy, respectively. Conclusion The FPA technique was retrospectively validated in a swine model and has the potential to be used for accurate, low-dose vessel-specific morphologic and physiologic assessment of coronary artery disease. © RSNA, 2017.

Drug-Eluting Embolic Loaded with Tyrosine Kinase Inhibitor Targeted Therapies for Transarterial Chemoembolization in a VX2 Model.

Drug-eluting embolic transarterial chemoembolization (DEE-TACE) improves the overall survival of hepatocellular carcinoma (HCC), but the agents used are not tailored to HCC. Our patented liposomal formulation enables the loading and elution of targeted therapies onto DEEs. This study aimed to establish the safety, feasibility, and pharmacokinetics of sorafenib or regorafenib DEE-TACE in a VX2 model. DEE-TACE was performed in VX2 hepatic tumors in a selective manner until stasis using liposomal sorafenib- or regorafenib-loaded DEEs. The animals were euthanized at 1, 24, and 72 h timepoints post embolization. Blood samples were taken for pharmacokinetics at 5 and 20 min and at 1, 24, and 72 h. Measurements of sorafenib or regorafenib were performed in all tissue samples on explanted hepatic tissue using the same mass spectrometry method. Histopathological examinations were carried out on tumor tissues and non-embolized hepatic specimens. DEE-TACE was performed on 23 rabbits. The plasma concentrations of sorafenib and regorafenib were statistically significantly several folds lower than the embolized liver at all examined timepoints. This study demonstrates the feasibility of loading sorafenib or regorafenib onto commercially available DEEs for use in TACE. The drugs eluted locally without release into systemic circulation.

Clinical presentation and outcomes after endovascular management in a mixed pediatric and adult Klippel-Trenaunay syndrome population.

OBJECTIVE: We retrospectively studied the clinical presentations and outcomes of endovascular management in a mixed pediatric and adult Klippel-Trenaunay syndrome (KTS) population at a single academic medical center. METHODS: We performed a retrospective study of patients with KTS who had been referred for endovascular intervention after evaluation and diagnosis by a multidisciplinary team at a single academic medical center during a 10-year period. The patient demographics, areas affected, presenting symptoms, previous treatments, imaging modalities, endovascular treatment types, number of treatments, and complications were assessed. The technical and clinical success rates were calculated. RESULTS: Twenty-six patients with suspected KTS were evaluated. Of these 26 patients, 20, aged 2 to 75 years, had been diagnosed with KTS using the International Society for the Study of Vascular Anomalies criteria and referred for endovascular management. The left lower extremity was affected most often. The presenting symptoms were pain (80%), edema (70%), bleeding (10%), numbness (25%), and claudication (25%). Of the 20 patients, 16 (80%) had undergone treatment of KTS before presenting to our institution. Magnetic resonance imaging and ultrasound (US) were the most common imaging modalities. Fifteen patients underwent 46 endovascular treatments during the study period. The treatments included 5 endovenous ablations only, 4 US-guided sclerotherapies with endovenous ablation, 5 US-guided sclerotherapies only, and 32 catheter-directed venograms with additional interventions. Localized intravascular coagulopathy was the only procedure-related complication and occurred in one patient after three treatments. The technical success rate was 97.8%, and the clinical success rate was 100%. CONCLUSIONS: Endovascular intervention is safe and effective for KTS patients for whom conservative management has failed. Pain and edema were the most common presenting symptoms. Presenting symptoms may be related to pathology of anomalous veins, orthotopic superficial veins or deep veins. Venous claudication can be present in those with KTS despite patency of the deep venous system. Magnetic resonance imaging and duplex US are frequently used modalities for venous assessment. The complications of endovascular treatment are rare but include localized intravascular coagulopathy.

Phase I Trial on Arterial Embolization with Hypoxia Activated Tirapazamine for Unresectable Hepatocellular Carcinoma.

BACKGROUND: Tirapazamine (TPZ) is a hypoxia activated drug that may be synergistic with transarterial embolization (TAE). The primary objective was to evaluate the safety of combining TPZ and TAE in patients with unresectable HCC and determine the optimal dose for Phase II. METHODS: This was a Phase 1 multicenter, open-label, non-randomized trial with a classic 3+3 dose escalation and an expansion cohort in patients with unresectable HCC, Child Pugh A, ECOG 0 or 1. Two initial cohorts consisted of I.V. administration of Tirapazamine followed by superselective TAE while the remaining three cohorts underwent intraarterial administration of Tirapazamine with superselective TAE. Safety and tolerability were assessed using NCI CTCAE 4.0 with clinical, imaging and laboratory examinations including pharmacokinetic (PK) analysis and an electrocardiogram 1 day pre-dose, at 1, 2, 4, 6, 10, and 24 hours post-TPZ infusion and an additional PK at 15- and 30-minutes post-TPZ. Tumor responses were evaluated using mRECIST criteria. RESULTS: Twenty-seven patients (mean [range] age of 66.4 [37-79] years) with unresectable HCC were enrolled between July 2015 and January 2018. Two patients were lost to follow-up. Mean tumor size was 6.53 cm ± 2.60 cm with a median of two lesions per patient. Dose limiting toxicity and maximum tolerated dose were not reached. The maximal TPZ dose was 10 mg/m2 I.V. and 20 mg/m2 I.A. One adverse event (AE) was reported in all patients with fatigue, decreased appetite or pain being most common. Grade 3-5 AE were hypertension and transient elevation of AST/ALT in 70.4% of patients. No serious AE were drug related. Sixty percent (95% CI=38.7-78.9) achieved complete response (CR), and 84% (95% CI=63.9-95.5) had complete and partial response per mRECIST for target lesions. DISCUSSION: TAE with TPZ was safe and tolerable with encouraging results justifying pursuit of a Phase II trial.

Therapy in Advanced Hepatocellular Carcinoma.

Treatment of advanced hepatocellular carcinoma (HCC) is challenging. Several randomized clinical trials are investigating the efficacy of systemic therapy, immunotherapy, and locoregional therapy as monotherapy or combined with other modalities in the treatment of HCC. Systemic therapy is the preferred treatment in advanced disease. To date, multiple first-line and second-line agents received Food and Drug Administration approval. For over a decade, sorafenib was the only first-line agent. In May 2020, combination of atezolizumab and bevacizumab has been approved as a first-line systemic regimen. Lenvatinib is another first-line agent that has multikinase activity. Second-line agents include cabozantinib, regorafenib, ramucirumab, and nivolumab. Adoptive cell transfer therapy is a highly specific immunotherapy that has shown antitumor activity against HCC. Oncolytic viruses are genetically modified viruses that infect cancer cells and induce apoptosis. Locoregional therapies such as transarterial chemoembolization and radioembolization have shown a potential benefit in selected patients with advanced HCC. In this review, we aim to summarize the treatment options available for advanced HCC.

Endovascular management of traumatic pseudoaneurysms.

BACKGROUND: Pseudoaneurysms (PAs) caused by traumatic injury to the arterial vasculature have a high risk of rupture, leading to life-threatening hemorrhage and mortality, requiring urgent treatment. The purpose of this study was to determine the technical and clinical outcomes of endovascular treatment of visceral and extremity traumatic pseudoaneurysms. METHODS: Clinical data were retrospectively collected from all patients presenting for endovascular treatment of PAs between September 2012 and September 2018 at a single academic level one trauma center. Technical success was defined as successful treatment of the PA with no residual filling on post-embolization angiogram. Clinical success was defined as technical successful treatment with no rebleeding throughout the follow-up period and no reintervention for the PA. RESULTS: Thirty-five patients (10F/25M), average age (± stdev) 41.7 ± 20.1 years, presented with PAs secondary to blunt (n = 31) or penetrating (n = 4) trauma. Time from trauma to intervention ranged from 2 h - 75 days (median: 4.4 h, IQR: 3.5-17.1 h) with 27 (77%) of PAs identified and treated within 24 h of trauma. Average hospitalization was 13.78 ± 13.4 days. Ten patients underwent surgery prior to intervention. PA number per patient ranged from 1 to 5 (multiple diffuse). PAs were located on the splenic (n = 12, 34.3%), pelvic (n = 11, 31.4%), hepatic (n = 9, 25.7%), upper extremity/axilla (n = 2, 5.7%), and renal arteries (n = 1, 2.9%). Technical success was 85.7%. Clinical success was 71.4%, for technical failure (n = 5), repeat embolization (n = 1) or post-IR surgical intervention (n = 4). There was no PA rebleeding or reintervention for any patient after discharge over the reported follow-up periods. Three patients died during the trauma hospitalization for reasons unrelated to the PAs. CONCLUSIONS: Endovascular treatment of traumatic visceral and extremity PAs is efficacious with minimal complication rates and low reintervention requirements.

MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease: cohort recruitment and baseline characteristics.

PURPOSE: MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease (MINERVA) was designed to answer the question of whether a novel continuous breast arterial calcification (BAC) mass score improves cardiovascular risk stratification among asymptomatic postmenopausal women. This article describes recruitment and baseline characteristics. METHODS: MINERVA is a multiethnic longitudinal cohort study. The phenotype data include BAC mass by densitometry applied to digital mammograms, sociodemographic factors, self-reported medical history, medications, parental history, reproductive history, smoking, alcohol consumption, physical activity, anthropometry, ankle-brachial index, blood pressure, laboratory panel, breast volumes, cognitive function, bioelectrical impedance, habitual diet, dietary supplements, sleep, psychosocial factors, and sun exposure. RESULTS: A total of 5145 women aged 60 to 79 years with available digital, uncompressed mammograms were recruited from the membership of Kaiser Permanente of Northern California between October 24, 2012 and February 13, 2015 and completed a baseline clinic visit or an abbreviated phone questionnaire. Of those, 4153 underwent phlebotomy and have blood biomarkers. Overall prevalence of BAC was 26%, and it varied by age and race. The mean (SD) BAC mass was 12 (23) mg and the range 0-342 mg. CONCLUSIONS: MINERVA is the first cohort with a continuous measure of BAC. The cohort is large, ethnically diverse, and deeply phenotyped in terms of socioeconomic, behavioral, and clinical factors, and blood biomarkers.

Functional Assessment of Coronary Artery Disease Using Whole-Heart Dynamic Computed Tomographic Perfusion.

BACKGROUND: Computed tomographic (CT) angiography is an important tool for the evaluation of coronary artery disease but often correlates poorly with myocardial ischemia. Current dynamic CT perfusion techniques can assess ischemia but have limited accuracy and deliver high radiation dose. Therefore, an accurate, low-dose, dynamic CT perfusion technique is needed. METHODS AND RESULTS: A total of 20 contrast-enhanced CT volume scans were acquired in 5 swine (40±10 kg) to generate CT angiography and perfusion images. Varying degrees of stenosis were induced using a balloon catheter in the proximal left anterior descending coronary artery, and a pressure wire was used for reference fractional flow reserve (FFR) measurement. Perfusion measurements were made with only 2 volume scans using a new first-pass analysis (FPA) technique and with 20 volume scans using an existing maximum slope model (MSM) technique. Perfusion (P) and FFR measurements were related by PFPA=1.01 FFR-0.03 (R2=0.85) and PMSM=1.03 FFR-0.03 (R2=0.80) for FPA and MSM techniques, respectively. Additionally, the effective radiation doses were calculated to be 2.64 and 26.4 mSv for FPA and MSM techniques, respectively. CONCLUSIONS: A new FPA-based dynamic CT perfusion technique was validated in a swine animal model. The results indicate that the FPA technique can potentially be used for improved anatomical and functional assessment of coronary artery disease at a relatively low radiation dose.