Publications

2021

Sarwar, Ammar, Alexei Kudla, Jeffrey L Weinstein, Aamir Ali, Raza Malik, Andrea Bullock, Khalid O Khwaja, Michael Curry, Salomao Faintuch, and Muneeb Ahmed. (2021) 2021. “Yttrium-90 Radioembolization Using MIRD Dosimetry With Resin Microspheres.”. European Radiology 31 (3): 1316-24. https://doi.org/10.1007/s00330-020-07231-8.

OBJECTIVE: To review the technical feasibility of resin microsphere (SIR-Spheres®) yttrium-90 radioembolization prescribed using the medical internal radiation dose (MIRD) model.

METHODS: All radioembolization procedures for hepatic malignancies using resin microspheres with MIRD model between November 2015 and February 2019 were included in this IRB-approved study (n = 60). Student's T test was used to compare prescribed activity based on MIRD and BSA models. Adverse events were assessed immediately, 30 days, and 6 months post-treatment.

RESULTS: Sixty radioembolizations were performed in 54 patients (age 68 ± 9 years, 48-87 years, 35% female). Mean prescribed activity calculated by the MIRD model (target absorbed dose 120-200 Gy for primary and 80-200 Gy for metastatic liver cancers) was 1.7 GBq (0.3-6.4) compared with 0.6 GBq (0.12-2.1) if BSA had been used (p < 0.0001). The prescribed activity was successfully delivered in 93% (56/60) treatments. Prophylactic embolization and anti-reflux catheters were used in 20% (12/60) and 5% (3/60) treatments, respectively. No immediate post-procedural complications occurred. Abdominal pain was the most common clinical Grade 3 CTCAE in 30 days (10%) and 6 months (12%). Radiation pneumonitis occurred in 3 (5%) patients but no radiation-induced gastric ulcer or radiation-induced liver disease occurred.

CONCLUSION: MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry with resin microspheres. MIRD prescribed activity with target absorbed doses up to 200 Gy can be successfully administered without prophylactic embolization in selected patients.

KEY POINTS: •MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry for radioembolization. •MIRD dosimetry can be used for yttrium-90 resin microsphere radioembolization with acceptable safety profile.

Thavikulwat, Amalie C, Jim S Wu, Xiaohe Chen, Megan E Anderson, Ashley Ward, and Justin Kung. (2021) 2021. “Image-Guided Core Needle Biopsy of Adipocytic Tumors: Diagnostic Accuracy and Concordance With Final Surgical Pathology.”. AJR. American Journal of Roentgenology 216 (4): 997-1002. https://doi.org/10.2214/AJR.20.23080.

OBJECTIVE. Diagnostic accuracy of core needle biopsy (CNB) for adipocytic tumors can be low because of sampling error from these often large, heterogeneous lesions. The purpose of this study was to evaluate the diagnostic accuracy of image-guided CNB for various adipocytic tumors in comparison with excisional pathology. MATERIALS AND METHODS. Adipocytic tumors (n = 77) of all adult patients undergoing image-guided CNB and subsequent surgical excision of an adipocytic tumor at a tertiary referral center between 2005 and 2019 were studied. To determine concordance, we compared pathologic diagnoses based on CNB to the reference standard of pathologic diagnoses after surgical excision. Tumors were divided into three categories (benign lipomatous tumors [lipoma, lipoma variants, hibernomas], atypical lipomatous tumors [ALTs] or well-differentiated liposarcomas [WDLs], and higher grade liposarcomas [myxoid, dedifferentiated, pleomorphic]), and diagnostic accuracy was calculated for each category. RESULTS. In 73 of 77 adipocytic tumors (95%), diagnosis at CNB and diagnosis after excision were concordant. Accuracy of diagnosis was poorer for ALTs and WDLs than for the other two categories, and the difference was statistically significant (p < .002). For the 29 benign lipomatous tumors and the 27 higher-grade liposarcomas, diagnoses at CNB and after excision were concordant in all cases (100%). Seventeen of the 21 tumors (81%) diagnosed as ALTs or WDLs at CNB had a concordant diagnosis after excision; four of the 21 were upgraded (dedifferentiated liposarcoma, n = 3; myxoid liposarcoma, n = 1). CONCLUSION. CNB provides high diagnostic accuracy for adipocytic tumors, particularly for benign lipomatous tumors and higher grade liposarcomas. However, though still high at 81%, diagnostic accuracy of CNB is not as high for tumors diagnosed as ALTs or WDLs. Awareness of this limitation is important when determining management, particularly of cases of ALT or WDL for which surgery is not planned.

Markezana, Aurelia, Nahum Goldberg, Gaurav Kumar, Elina Zorde-Khvalevsky, Svetlana Gourevtich, Nir Rozenblum, Eithan Galun, and Muneeb Ahmed. (2021) 2021. “Incomplete Thermal Ablation of Tumors Promotes Increased Tumorigenesis.”. International Journal of Hyperthermia : The Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 38 (1): 263-72. https://doi.org/10.1080/02656736.2021.1887942.

PURPOSE: While systemic tumor-stimulating effects can occur following ablation of normal liver linked to the IL-6/HGF/VEGF cytokinetic pathway, the potential for tumor cells themselves to produce these unwanted effects is currently unknown. Here, we study whether partially treated tumors induce increased tumor growth post-radiofrequency thermal ablation (RFA).

METHODS: Tumor growth was measured in three immunocompetent, syngeneic tumor models following partial RFA of the target tumor (in subcutaneous CT26 and MC38 mouse colorectal adenocarcinoma, N = 14 each); and in a distant untreated tumor following partial RFA of target subcutaneous R3230 rat breast adenocarcinoma (N = 12). Tumor cell proliferation (ki-67) and microvascular density (CD34) was assessed. In R3230 tumors, in vivo mechanism of action was assessed following partial RFA by measuring IL-6, HGF, and VEGF expression (ELISA) and c-Met protein (Western blot). Finally, RFA was performed in R3230 tumors with adjuvant c-Met kinase inhibitor or VEGF receptor inhibitor (at 3 days post-RFA, N = 3/arm, total N = 12).

RESULTS: RFA stimulated tumor growth in vivo in residual, incompletely treated surrounding CT26 and MC38 tumor at 3-6 days (p < 0.01). In R3230, RFA increased tumor growth in distant tumor 7 days post treatment compared to controls (p < 0.001). For all models, Ki-67 and CD34 were elevated (p < 0.01, all comparisons). IL-6, HGF, and VEGF were also upregulated post incomplete tumor RFA (p < 0.01). These markers were suppressed to baseline levels with adjuvant c-MET kinase or VEGF receptor inhibition.

CONCLUSION: Incomplete RFA of a target tumor can sufficiently stimulate residual tumor cells to induce accelerated growth of distant tumors via the IL-6/c-Met/HGF pathway and VEGF production.

Gaube, Susanne, Harini Suresh, Martina Raue, Alexander Merritt, Seth J Berkowitz, Eva Lermer, Joseph F Coughlin, John Guttag V, Errol Colak, and Marzyeh Ghassemi. (2021) 2021. “Do As AI Say: Susceptibility in Deployment of Clinical Decision-Aids.”. NPJ Digital Medicine 4 (1): 31. https://doi.org/10.1038/s41746-021-00385-9.

Artificial intelligence (AI) models for decision support have been developed for clinical settings such as radiology, but little work evaluates the potential impact of such systems. In this study, physicians received chest X-rays and diagnostic advice, some of which was inaccurate, and were asked to evaluate advice quality and make diagnoses. All advice was generated by human experts, but some was labeled as coming from an AI system. As a group, radiologists rated advice as lower quality when it appeared to come from an AI system; physicians with less task-expertise did not. Diagnostic accuracy was significantly worse when participants received inaccurate advice, regardless of the purported source. This work raises important considerations for how advice, AI and non-AI, should be deployed in clinical environments.

Satyam, Abhigyan, Maria G Tsokos, Olga R Brook, Jonathan L Hecht, Vaishali R Moulton, and George C Tsokos. (2021) 2021. “Activation of Classical and Alternative Complement Pathways in the Pathogenesis of Lung Injury in COVID-19.”. Clinical Immunology (Orlando, Fla.) 226: 108716. https://doi.org/10.1016/j.clim.2021.108716.

Lung inflammation and damage is prominent in people infected with SARS-Cov-2 and a major determinant of morbidity and mortality. We report the deposition of complement components in the lungs of people who succumbed to COVID-19 consistent with the activation of the classical and the alternative pathways. Our study provides strong rationale for the expansion of trials involving the use of complement inhibitors to treat patients with COVID-19.

Alkalay, Ron N, Robert Adamson, Alexander Miropolsky, Roger B Davis, Mike L Groff, and David B Hackney. (2021) 2021. “Large Lytic Defects Produce Kinematic Instability and Loss of Compressive Strength in Human Spines: An in Vitro Study.”. The Journal of Bone and Joint Surgery. American Volume 103 (10): 887-99. https://doi.org/10.2106/JBJS.19.00419.

BACKGROUND: In patients with spinal metastases, kinematic instability is postulated to be a predictor of pathologic vertebral fractures. However, the relationship between this kinematic instability and the loss of spinal strength remains unknown.

METHODS: Twenty-four 3-level thoracic and lumbar segments from 8 cadaver spines from female donors aged 47 to 69 years were kinematically assessed in axial compression (180 N) and axial compression with a flexion or extension moment (7.5 Nm). Two patterns of lytic defects were mechanically simulated: (1) a vertebral body defect, corresponding to Taneichi model C (n = 13); and (2) the model-C defect plus destruction of the ipsilateral pedicle and facet joint, corresponding to Taneichi model E (n = 11). The kinematic response was retested, and compression strength was measured. Two-way repeated-measures analysis of variance was used to test the effect of each model on the kinematic response of the segment. Multivariable linear regression was used to test the association between the kinematic parameters and compressive strength of the segment.

RESULTS: Under a flexion moment, and for both models C and E, the lesioned spines exhibited greater flexion range of motion (ROM) and axial translation than the control spines. Both models C and E caused lower extension ROM and greater axial, sagittal, and transverse translation under an extension moment compared with the control spines. Two-way repeated-measures analysis revealed that model E, compared with model C, caused significantly greater changes in extension and torsional ROM under an extension moment, and greater sagittal translation under a flexion moment. For both models C and E, greater differences in flexion ROM and sagittal translation under a flexion moment, and greater differences in extension ROM and in axial and transverse translation under an extension moment, were associated with lower compressive strength of the lesioned spines.

CONCLUSIONS: Critical spinal lytic defects result in kinematic abnormalities and lower the compressive strength of the spine.

CLINICAL RELEVANCE: This experimental study demonstrates that lytic foci degrade the kinematic stability and compressive strength of the spine. Understanding the mechanisms for this degradation will help to guide treatment decisions that address inferred instability and fracture risk in patients with metastatic spinal disease.

Sarwar, Ammar, Anthony M Esparaz, Nihara Chakrala, Mark Mangano, Suvranu Ganguli, Raza Malik, and Muneeb Ahmed. (2021) 2021. “Efficacy of TIPS Reduction for Refractory Hepatic Encephalopathy, Right Heart Failure, and Liver Dysfunction.”. AJR. American Journal of Roentgenology 216 (5): 1267-72. https://doi.org/10.2214/AJR.19.22497.

OBJECTIVE. The purpose of this study was to determine clinical outcomes of patients undergoing TIPS reduction. MATERIALS AND METHODS. In this institutional review board-approved, HIPAA-compliant study, all TIPS reductions performed at two institutions from January 1, 2008 to January 31, 2016, were retrospectively identified. Patients were divided into two groups according to pre-TIPS symptoms: volume overload due to ascites or hydrothorax (VO; n = 14) or variceal bleeding (VB; n = 12). Patient demographics, pre-TIPS model for end-stage liver disease score, pre- and post-TIPS portosystemic gradients, and clinical parameters were recorded. The primary endpoint was change in symptoms of hepatic encephalopathy (HE; West Haven criteria), right heart failure, or liver dysfunction. Secondary endpoints included paracentesis rate for the VO group and rebleeding for the VB group. RESULTS. The degree of HE increased in 24 of 26 patients (92%) after TIPS placement and decreased in 24 of 26 patients (92%) after TIPS reduction. Mean West Haven scores for the VO group decreased after TIPS reduction (from 2.57 ± 0.97 [SD] to 1.07 ± 0.70; p < .001). Mean West Haven scores for the VB group also decreased after TIPS reduction (from 2.45 ± 0.89 to 1.27 ± 0.86; p = .007). Right heart failure improved in two of three patients (67%), and total bilirubin improved in one of three patients (33%). Follow-up data were available up to median of 134 days (interquartile range, 44-286). TIPS reduction led to an increased paracentesis rate compared with before TIPS placement in four of 14 patients with VO (29%). One patient had a stable paracentesis rate after TIPS reduction compared with before TIPS placement. Variceal rebleeding did not occur in any patients with VB after TIPS reduction. At 54 days after TIPS reduction, one of the 12 patients with VB (9%) experienced hematemesis due to an endoscopically proven band-related ulcer. CONCLUSION. TIPS reduction successfully resolved HE and refractory right heart failure in most patients. In patients with VB, TIPS reduction with variceal embolization results in a low risk of short-term recurrent VB. However, in patients with VO, ascites may return or worsen after TIPS reduction despite improvement in HE.

Tsai, Leo L, Rupal S Bhatt, Meaghan F Strob, Opeyemi A Jegede, Maryellen R M Sun, David C Alsop, Paul Catalano, et al. (2021) 2021. “Arterial Spin Labeled Perfusion MRI for the Evaluation of Response to Tyrosine Kinase Inhibition Therapy in Metastatic Renal Cell Carcinoma.”. Radiology 298 (2): 332-40. https://doi.org/10.1148/radiol.2020201763.

Background Tumor perfusion may inform therapeutic response and resistance in metastatic renal cell carcinoma (RCC) treated with antiangiogenic therapy. Purpose To determine if arterial spin labeled (ASL) MRI perfusion changes are associated with tumor response and disease progression in metastatic RCC treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Materials and Methods In this prospective study (ClinicalTrials.gov identifier: NCT00749320), metastatic RCC perfusion was measured with ASL MRI before and during sunitinib or pazopanib therapy between October 2008 and March 2014. Objective response rate (ORR) and progression-free survival (PFS) were calculated. Perfusion was compared between responders and nonresponders at baseline, at week 2, after cycle 2 (12 weeks), after cycle 4 (24 weeks), and at disease progression and compared with the ORR by using the Wilcoxon rank sum test and with PFS by using the log-rank test. Results Seventeen participants received sunitinib (mean age, 59 years ± 7.0 [standard deviation]; 11 men); 11 participants received pazopanib (mean age, 63 years ± 6.6; eight men). Responders had higher baseline tumor perfusion than nonresponders (mean, 404 mL/100 g/min ± 213 vs 199 mL/100 g/min ± 136; P = .02). Perfusion decreased from baseline to week 2 (-53 mL/100 g/min ± 31; P < .001), after cycle 2 (-65 mL/100 g/min ± 25; P < .001), and after cycle 4 (-79 mL/100 g/min ± 15; P = .008). Interval reduction in perfusion at those three time points was not associated with ORR (P = .63, .29, and .27, respectively) or PFS (P = .28, .27, and .32). Perfusion increased from cycle 4 to disease progression (51% ± 11; P < .001). Conclusion Arterial spin labeled perfusion MRI may assist in identifying responders to vascular endothelial growth factor receptor tyrosine kinase inhibitors and may help detect early evidence of disease progression in patients with metastatic renal cell carcinoma. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Goh and De Vita in this issue.

Weinstein, Jeffrey L, Fady El-Gabalawy, Ammar Sarwar, Sarah Schroeppel DeBacker, Salomao Faintuch, Seth J Berkowitz, Julie C Bulman, et al. (2021) 2021. “Analysis of Kinematic Differences in Hand Motion Between Novice and Experienced Operators in IR: A Pilot Study.”. Journal of Vascular and Interventional Radiology : JVIR 32 (2): 226-34. https://doi.org/10.1016/j.jvir.2020.10.010.

PURPOSE: To prospectively validate electromagnetic hand motion tracking in interventional radiology to detect differences in operator experience using simulation.

METHODS: Sheath task: Six attending interventional radiologists (experts) and 6 radiology trainees (trainees) placed a wire through a sheath and performed a "pin-pull" maneuver, while an electromagnetic motion detection system recorded the hand motion. Radial task: Eight experts and 12 trainees performed palpatory radial artery access task on a radial access simulator. The trainees repeated the task with the nondominant hand. The experts were classified by their most frequent radial artery access technique as having either palpatory, ultrasound, or overall limited experience. The time, path length, and number of movements were calculated. Mann-Whitney U tests were used to compare the groups, and P < .05 was considered significant.

RESULTS: Sheath task: The experts took less time, had shorter path lengths, and used fewer movements than the trainees (11.7 seconds ± 3.3 vs 19.7 seconds ± 6.5, P < .01; 1.1 m ± 0.3 vs 1.4 m ± 0.4, P < .01; and 19.5 movements ± 8.5 vs 31.0 movements ± 8.0, P < .01, respectively). Radial task: The experts took less time, had shorter path lengths, and used fewer movements than the trainees (24.2 seconds ± 10.6 vs 33.1 seconds ± 16.9, P < .01; 2.0 m ± 0.5 vs 3.0 m ± 1.9, P < .001; and 36.5 movements ± 15.0 vs 54.5 movements ± 28.0, P < .001, respectively). The trainees had a shorter path length for their dominant hand than their nondominant hand (3.0 m ± 1.9 vs 3.5 m ± 1.9, P < .05). The expert palpatory group had a shorter path length than the ultrasound and limited experience groups (1.8 m ± 0.4 vs 2.0 m ± 0.4 and 2.3 m ± 1.2, respectively, P < .05).

CONCLUSIONS: Electromagnetic hand motion tracking can differentiate between the expert and trainee operators for simulated interventional tasks.