Distinguishing Intrathyroid Parathyroid Adenoma from Colloid Nodules and Papillary Thyroid Carcinomas Using Multiphasic Multidetector Computed Tomography.

OBJECTIVE: The aim of the study is to determine whether multiphase multidetector computed tomography (4D-MDCT) can differentiate between intrathyroid parathyroid adenomas (ITPAs), colloid nodules, and papillary thyroid carcinoma (PTC). METHODS: We studied 22 ITPAs, 22 colloid nodules, and 11 PTCs in 55 patients. Hounsfield unit (HU) values of the nodules were measured on 4D-MDCT in the precontrast, arterial, venous, and delayed phases. Raw HU values, phase with peak enhancement, and washout percentages between the phases were evaluated. RESULTS: Regardless of size, all ITPAs (22/22) showed peak enhancement in the arterial phase, which was significantly greater than both colloid nodules (15/22) and PTC (6/11, P = 0.002); thus, nodules with peak enhancement in the venous or delayed phase were not ITPAs (specificity = 1). For nodules with peak enhancement in the arterial phase, the percentage washout in the arterial-to-venous phases separated ITPAs from PTC and colloid nodules (P < 0.001) with greater than or equal to 23.95% loss of HU value implying IPTA (area under curve, 0.79). This left a subset of colloid nodules or PTC that either peaked in the venous or delayed phase or had an arterial-to-venous phase washout of less than 23.95%. From this subset, PTC measuring 1 cm or greater could be separated from colloid based on HU values in the arterial phase with a cutoff HU value less than 81.4 for PTC (area under curve, 0.72) and an HU value greater than 164.5 suggested colloid. CONCLUSIONS: Intrathyroid parathyroid adenomas can be distinguished from colloid nodules and PTC by peak enhancement in the arterial phase and rapid washout. A subset of colloid and PTC measuring 1 cm or greater can be separated using arterial phase HU values.

Management of a patient with mantle cell lymphoma who developed severe neurotoxicity after chimeric antigen receptor T-cell therapy in ZUMA-2.

Cerebral edema following chimeric antigen receptor (CAR) T-cell therapy can be fatal. ZUMA-2 is a pivotal phase 2, multicenter study evaluating KTE-X19, an autologous anti-CD19 CAR T-cell therapy, in relapsed/refractory mantle cell lymphoma. We describe a 65-year-old patient in ZUMA-2 who developed cerebral edema following CAR T-cell therapy and had complete recovery after multimodality clinical intervention including rabbit antithymocyte globulin (ATG). Biomarker results show early and robust CAR T-cell expansion and related induction of inflammatory cytokines, followed by rapid declines in CAR T-cell and proinflammatory cytokine levels after ATG administration. This clinical profile highlights a potential relevance of ATG in treating severe CAR T-cell-related neurotoxicity.

Clinical and radiologic correlates of neurotoxicity after axicabtagene ciloleucel in large B-cell lymphoma.

Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an objective grading system. Neuroimaging studies and electroencephalograms (EEGs) were reviewed by an expert neuroradiologist and neurologist. Of 100 patients included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had grade ≥3. Median time to ICANS onset was 5 days, and median duration was 6 days. ICANS grade ≥3 was associated with high peak ferritin (P = .03) and C-reactive protein (P = .001) levels and a low peak monocyte count (P = .001) within the 30 days after axi-cel infusion. Magnetic resonance imaging was performed in 38 patients with ICANS and revealed 4 imaging patterns with features of encephalitis (n = 7), stroke (n = 3), leptomeningeal disease (n = 2), and posterior reversible encephalopathy syndrome (n = 2). Abnormalities noted on EEG included diffuse slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status epilepticus (n = 8). Although reversible, grade ≥3 ICANS was associated with significantly shorter progression-free (P = .02) and overall survival (progression being the most common cause of death; P = .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.

Early imaging marker of progressing glioblastoma: a window of opportunity.

PURPOSE: Therapeutic intervention at glioblastoma (GBM) progression, as defined by current assessment criteria, is arguably too late as second-line therapies fail to extend survival. Still, most GBM trials target recurrent disease. We propose integration of a novel imaging biomarker to more confidently and promptly define progression and propose a critical timepoint for earlier intervention to extend therapeutic exposure. METHODS: A retrospective review of 609 GBM patients between 2006 and 2019 yielded 135 meeting resection, clinical, and imaging inclusion criteria. We qualitatively and quantitatively analyzed 2000+ sequential brain MRIs (initial diagnosis to first progression) for development of T2 FLAIR signal intensity (SI) within the resection cavity (RC) compared to the ventricles (V) for quantitative inter-image normalization. PFS and OS were evaluated using Kaplan-Meier curves stratified by SI. Specificity and sensitivity were determined using a 2 × 2 table and pathology confirmation at progression. Multivariate analysis evaluated SI effect on the hazard rate for death after adjusting for established prognostic covariates. Recursive partitioning determined successive quantifiers and cutoffs associated with outcomes. Neurological deficits correlated with SI. RESULTS: Seventy-five percent of patients developed SI on average 3.4 months before RANO-assessed progression with 84% sensitivity. SI-positivity portended neurological decline and significantly poorer outcomes for PFS (median, 10 vs. 15 months) and OS (median, 20 vs. 29 months) compared to SI-negative. RC/V ratio ≥ 4 was the most significant prognostic indicator of death. CONCLUSION: Implications of these data are far-reaching, potentially shifting paradigms for glioma treatment response assessment, altering timepoints for salvage therapeutic intervention, and reshaping glioma clinical trial design.

Ventricular apparent diffusion coefficient measurements in patients with neoplastic leptomeningeal disease.

BACKGROUND: To test the hypothesis that intraventricular ADC values can be used to determine the presence of neoplastic leptomeningeal disease (LMD). MATERIALS AND METHODS: ADC values were measured at multiple sites in the ventricular system in 32 patients with cytologically-proven LMD and 40 control subjects. Multiple linear regression analysis was used to determine the mean difference of ADCs between the LMD and control groups after adjusting for ventricle size and tumor type. Receiver operating characteristics (ROC) analysis was performed and optimal ADC value cut-off point for predicting the presence of LMD. ADC was compared to T1 enhancement and FLAIR signal hyperintensity for determining the presence of LMD. RESULTS: After adjusting for ventricular volume and tumor type, the mid body of lateral ventricles showed no significant difference in ventricular volume and a significant difference in ADC values between the control and LMD groups (p > 0.05). In the mid-body of the right lateral ventricle the AUC was 0.69 (95% CI 0.57-0.81) with an optimal ADC cut off point of 3.22 × 10- 9 m2/s (sensitivity, specificity; 0.72, 0.68). In the mid-body of left lateral ventricle the AUC was 0.7 (95% CI 0.58-0.82) with an optimal cut-off point of 3.23 × 10- 9 m2/s (0.81, 0.62). Using an average value of HU measurements in the lateral ventricles the AUC was 0.73 (95% CI 0.61-0.84) with an optimal cut off point was 3.11 × 10- 9 m2/s (0.78, 0.65). Compared to the T1 post-contrast series, ADC was predictive of the presence of LMD in the mid-body of the left lateral ventricle (p = 0.036). CONCLUSION: Complex interactions affect ADC measurements in patients with LMD. ADC values in the lateral ventricles may provide non-invasive clues to the presence of LMD.

Allogeneic BK Virus-Specific T Cells for Progressive Multifocal Leukoencephalopathy.

JC virus, the cause of progressive multifocal leukoencephalopathy (PML), and the BK virus are genetically similar and share sequence homology in immunogenic proteins. We treated three immunosuppressed patients with PML with ex vivo-expanded, partially HLA-matched, third-party-produced, cryopreserved BK virus-specific T cells. The immunosuppression in these patients was due to the conditioning regimen for cord-blood transplantation in one patient, a myeloproliferative neoplasm treated with ruxolitinib in another, and acquired immunodeficiency syndrome in the third. After T-cell infusion in two of the patients, alleviation of the clinical signs and imaging features of PML was seen and JC virus in the cerebrospinal fluid (CSF) cleared. The other patient had a reduction in JC viral load and stabilization of symptoms that persisted until her death 8 months after the first infusion. Two of the patients had immune reconstitution syndrome. Donor-derived T cells were detected in the CSF after infusion. (Funded by the M.D. Anderson Cancer Center Moon Shots Program and the National Institutes of Health; ClinicalTrials.gov number, NCT02479698 .).

Dynamic contrast-enhanced MRI of orbital and anterior visual pathway lesions.

PURPOSE: The accurate diagnosis of orbital and anterior visual pathway lesions has clinical significance. We determined whether dynamic contrast-enhanced MRI could differentiate benign from malignant lesions and compared model-independent and model-dependent methods of data analysis. METHODS: We retrospectively reviewed dynamic contrast-enhanced MRI studies of 37 enhancing orbital and anterior visual pathway lesions. The data were processed using model-independent analysis and model-dependent analysis using a 2-compartment pharmacokinetic model. The time-signal intensity curve and semiquantitative parameters from the model-independent method (area under the curve [AUC] after the initial 60, 90, and 120 s; time to peak; maximum signal enhancement ratio; maximum slope of increase; and washout ratio) and the quantitative parameters from the model-dependent method (Ktrans, kep, and ve) were derived for comparison with pathologic diagnoses. RESULTS: The time-signal intensity curves demonstrated different perfusion characteristics and were classified into 4 types. All the lesions that demonstrated curve types 1 and 4 were benign, while type 3 lesions were significantly associated with malignancy (P = 0.001). AUC60, AUC90, AUC120, and kep were significantly lower in benign lesions than in malignant lesions (P = 0.020, 0.018, 0.015, and 0.018, respectively). Receiver operating characteristic analysis indicated that AUC120 yielded the best diagnostic accuracy (area under the curve, 0.80; 95% CI, 0.64-0.96) in differentiating between benign and malignant lesions. CONCLUSIONS: Dynamic contrast-enhanced MRI is useful in evaluating orbital and anterior visual pathway lesions. The model-independent analysis method is equivalent to the model-dependent method in differentiating benign from malignant lesions.

Radiation Therapy as an Effective Salvage Strategy for Secondary CNS Lymphoma.

PURPOSE: We assessed the efficacy of radiation therapy (RT) in the management of secondary central nervous system (CNS) lymphoma. METHODS AND MATERIALS: The cohort comprised 44 patients with systemic diffuse large B-cell lymphoma (DLBCL) secondarily involving the brain and/or leptomeninges at initial diagnosis or relapse that was treated with RT. RESULTS: Of these patients, 29 (66%) were in systemic remission when CNS disease was diagnosed. The overall response rate to RT by magnetic resonance imaging was 88% (42% complete, 46% partial). The median overall survival (OS) after RT initiation was 7 months (95% confidence interval 4-10 months). The OS curve plateaued at 31% from 2 to 8 years. OS was superior in patients who achieved a complete or partial response to RT, underwent stem cell transplantation after RT, and had brain parenchymal (vs leptomeningeal) disease. Eight cases of CNS disease progression occurred after RT: 1 involved the brain parenchyma, and 7 involved the spine and/or cerebrospinal fluid and/or meninges. CONCLUSIONS: We conclude that RT is associated with high response rates and may contribute to long-term OS. In addition, RT may provide CNS disease control that facilitates successful salvage with stem cell transplantation in patients with chemotherapy-refractory disease.

Most common sites on MRI of intracranial neoplastic leptomeningeal disease.

Neoplastic leptomeningeal disease (LMD) represents infiltration of the leptomeninges by tumor cells. Knowledge of the frequencies of locations of LMD on MRI may assist in early detection, help elucidate the process of leptomeningeal spread of cancer and understand how LMD affects the central nervous system. Our goal was to identify intracranial sites of neoplastic LMD predilection on MRI in patients with cytologically-proven LMD. The presence of FLAIR signal hyperintensity and T1-weighted post-contrast enhancement in the sulci of the supratentorial compartment and cerebellum and enhancement of the cranial nerves (CNs), basal cisterns, pituitary stalk, and ependymal surface of the lateral ventricles, as well as the presence of parenchymal metastasis were recorded. Within each imaging sequence, sites were ordered by prevalence and compared using McNemar's test. The study included 270 patients. Positive MRI findings were present in 185/270 (68.5%) patients. FLAIR signal hyperintensity was significantly more common (p≤0.003) in the cerebellum (n=96) and occipital lobe (n=92) relative to the other lobes. Leptomeningeal enhancement was also significantly more common (p≤0.009) in the cerebellum (n=82) and occipital lobe (n=67) relative to the other lobes. Enhancement was most commonly found involving CN VII/VIII and the ependymal surface of the lateral ventricles compared to other sites. Parenchymal metastases were present in 110 (40.1%) of the patients. In conclusion, neoplastic LMD predominantly involves the cerebellum and occipital lobes, CN VII/VIII, and the ependymal lining of the lateral ventricles. Parenchymal metastases are frequently present in patients with neoplastic LMD.

Prognostic Role of Conventional and Dynamic Contrast-Enhanced MRI in Optic Pathway Gliomas.

BACKGROUND AND PURPOSE: The natural history of optic pathway glioma (OPG) is highly variable and unpredictable. We present a pilot study of the prognostic role of conventional and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) in the evaluation of OPG. METHODS: We retrospectively reviewed 17 patients with 20 pretreatment OPG lesions who underwent conventional and DCE MRI between January 2010 and December 2016. Conventional MRI was evaluated for enhancement pattern, cystic component, optic nerve tortuosity, optic nerve dural ectasia, and optic nerve perineural thickening. The DCE MRI data were analyzed for quantitative parameters using the two-compartment pharmacokinetic model (Ktrans , kep , and ve ) and for semiquantitative parameters based on time-signal intensity curve (AUC60 , peak, and wash-in). The results were compared with the clinically progressive or nonprogressive tumor. RESULTS: Five progressive OPGs and 15 nonprogressive OPGs were included. Conventional MRI findings of diffuse enhancement and cystic component were significantly correlated with progressive OPGs (both P = .01). Conventional MRI yielded sensitivity of 60%, specificity of 100%, and accuracy of 90%. Ktrans , kep , and ve as well as AUC60 , peak, and wash-in were significantly higher in progressive OPGs (P < .05). Using DCE MRI increased diagnostic performance up to a sensitivity of 100%, specificity of 93%, and accuracy of 95%. CONCLUSION: DCE MRI accurately distinguished progressive and nonprogressive OPGs, with high sensitivities and specificities. DCE MRI has a significant prognostic role in predicting progressive OPGs, thus making it useful for the identification of patients who need close clinical and imaging follow-up.

Use of Spinal Cord Diffusion Tensor Imaging to Quantify Neural Ablation and Evaluate Outcome after Percutaneous Cordotomy for Intractable Cancer Pain.

BACKGROUND: Up to 20% of patients experience only partial pain relief after percutaneous cordotomy for cancer pain. OBJECTIVE: To determine whether diffusion tensor imaging (DTI) can quantify neural ablation and help evaluate early postoperative outcomes after cordotomy. METHODS: Patients undergoing percutaneous CT-guided cordotomy for intractable cancer pain were prospectively studied. Pre- and postoperative assessment was made using the visual analog scale (VAS) on pain and the pain severity scores of the Brief Pain Inventory Short Form. On postoperative day 1, DTI images of the high cervical spinal cord were obtained. DTI metrics were correlated with the number of ablations as well as early postoperative pain outcomes. RESULTS: Seven patients (4 male, mean age 53.8 ± 4.6 years) were studied. Fractional anisotropy of the hemicord was significantly lower on the side of the lesion as compared to the contralateral side (0.54 ± 0.03 vs. 0.63 ± 0.03, p < 0.001). Mean diffusivity correlated with the improvement in the VAS score at 1 week (r = 0.88, 95% CI = 0.34-1.00, p = 0.008), as well as the change in pain severity scores at 1 week (r = 0.99, 95% CI = 0.82-1.00, p < 0.001). CONCLUSION: DTI metrics are sensitive to the number of ablations as well as early improvement in pain scores after cordotomy. DTI of the cervical spinal cord is a potential biomarker of neural ablation after percutaneous cordotomy for intractable cancer pain.

Orbital oncocytoma: evaluation with dynamic contrast-enhanced magnetic resonance imaging using a time-signal intensity curve and positive enhancement integral images.

Oncocytomas, which are benign epithelial tumors filled with abundant mitochondria, arise from ductal cells. Oncocytomas rarely occur in the orbit. We present a case of pathologically proven orbital oncocytoma of the lacrimal gland studied by dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). DCE MRI has potential as an adjunct to conventional MRI in the differential diagnosis and tumor margin delineation of orbital oncocytoma. Simple assessments of the time-signal intensity curve, semiquantitative parameters, and post-processing positive enhancement integral images should be considered in the evaluation of orbital masses found on MRI.

Diffusion MRI quality control and functional diffusion map results in ACRIN 6677/RTOG 0625: a multicenter, randomized, phase II trial of bevacizumab and chemotherapy in recurrent glioblastoma.

Functional diffusion mapping (fDM) is a cancer imaging technique that quantifies voxelwise changes in apparent diffusion coefficient (ADC). Previous studies have shown value of fDMs in bevacizumab therapy for recurrent glioblastoma multiforme (GBM). The aim of the present study was to implement explicit criteria for diffusion MRI quality control and independently evaluate fDM performance in a multicenter clinical trial (RTOG 0625/ACRIN 6677). A total of 123 patients were enrolled in the current multicenter trial and signed institutional review board-approved informed consent at their respective institutions. MRI was acquired prior to and 8 weeks following therapy. A 5-point QC scoring system was used to evaluate DWI quality. fDM performance was evaluated according to the correlation of these metrics with PFS and OS at the first follow-up time-point. Results showed ADC variability of 7.3% in NAWM and 10.5% in CSF. A total of 68% of patients had usable DWI data and 47% of patients had high quality DWI data when also excluding patients that progressed before the first follow-up. fDM performance was improved by using only the highest quality DWI. High pre-treatment contrast enhancing tumor volume was associated with shorter PFS and OS. A high volume fraction of increasing ADC after therapy was associated with shorter PFS, while a high volume fraction of decreasing ADC was associated with shorter OS. In summary, DWI in multicenter trials are currently of limited value due to image quality. Improvements in consistency of image quality in multicenter trials are necessary for further advancement of DWI biomarkers.

Early post-bevacizumab progression on contrast-enhanced MRI as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 Central Reader Study.

BACKGROUND: RTOG 0625/ACRIN 6677 is a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma (GBM). This study investigated whether early posttreatment progression on FLAIR or postcontrast MRI assessed by central reading predicts overall survival (OS). METHODS: Of 123 enrolled patients, 107 had baseline and at least 1 posttreatment MRI. Two central neuroradiologists serially measured bidimensional (2D) and volumetric (3D) enhancement on postcontrast T1-weighted images and volume of FLAIR hyperintensity. Progression status on all posttreatment MRIs was determined using Macdonald and RANO imaging threshold criteria, with a third neuroradiologist adjudicating discrepancies of both progression occurrence and timing. For each MRI pulse sequence, Kaplan-Meier survival estimates and log-rank test were used to compare OS between cases with or without radiologic progression. RESULTS: Radiologic progression occurred after 2 chemotherapy cycles (8 weeks) in 9 of 97 (9%), 9 of 73 (12%), and 11 of 98 (11%) 2D-T1, 3D-T1, and FLAIR cases, respectively, and 34 of 80 (43%), 21 of 58 (36%), and 37 of 79 (47%) corresponding cases after 4 cycles (16 weeks). Median OS among patients progressing at 8 or 16 weeks was significantly less than that among nonprogressors, as determined on 2D-T1 (114 vs 278 days and 214 vs 426 days, respectively; P < .0001 for both) and 3D-T1 (117 vs 306 days [P < .0001] and 223 vs 448 days [P = .0003], respectively) but not on FLAIR (201 vs 276 days [P = .38] and 303 vs 321 days [P = .13], respectively). CONCLUSION: Early progression on 2D-T1 and 3D-T1, but not FLAIR MRI, after 8 and 16 weeks of anti-vascular endothelial growth factor therapy has highly significant prognostic value for OS in recurrent GBM.

Co-registration of Sequential Multidetector Computed Tomography Studies for the Evaluation of Surgical Instrumentation following Resection of Spinal Tumors.

Surgical resection of spinal tumors involves complex reconstructive procedures. The stability and integrity of the surgical construct are evaluated with multidetector computed tomography (MDCT). As coregistration, or fusion, of different imaging modalities, especially positron emission tomography/computed tomography (PET/CT), is common practice, we sought to determine if this technique could be applied to sequential, postoperative MDCT studies of the spine. Herein, we demonstrate that by utilizing the Hermes workstation, co-registration of MDCT spine studies can be performed. This technique allows sequential MDCT examinations of the post-operative spine to be viewed together as one study and may aid in evaluation of the position and integrity of the surgical construct over time. Further study and refinement of this technique will be necessary before clinical implementation.

Developments in general airway management.

Since the 1970s, improvements in airway management have been significant. New imaging modalities such as CT and MRI can display airway structures with unparalleled detail, which improves preoperative planning and the treatment of patients with pathologic processes involving the respiratory tract or with difficult-to-manage airways. Because of the introduction of flexible fiberscopes, pulmonologists and thoracic surgeons can diagnose diseases of the respiratory tract effectively and treat patients with these diseases safely. The use of flexible fiberscopes has expanded rapidly into other medical specialties, including anesthesia and critical care. Modem anesthesiologists now use flexible fiberscopes daily to intubate patients safely, especially when traditional intubating techniques fail. The cost of fiberscopes has decreased dramatically, and their optical systems have improved. Several centers of excellence have been developed where clinicians can learn basic and advanced techniques of fiberoptic intubation. The LMA has shown that the supraglottic airway approach is not only feasible, but also in many situations superior to tracheal intubation. Although the LMA initially was recommended as an alternative to the facemask, its use has expanded, benefiting many children and adults undergoing a variety of diagnostic and therapeutic procedures. Use of an LMA in combination with a flexible fiberscope has opened up new possibilities for treating patients safely and effectively while providing optimal comfort during a procedure and has been particularly beneficial in thoracic surgery. The most recent iteration of the ASA Difficult Airway Algorithm has revised further a systematic approach to the clinical care of patients with different types of difficult-to-manage airways.