Effects of HIV on the Tumor Microenvironment.

Oncomodulatory viruses can affect the tumor microenvironment (TME) by triggering inflammation, suppressing apoptosis, initiating angiogenesis, altering tumor metabolism, and stimulating tumor cell signaling pathways, leading to tumor growth, proliferation, and invasion. The higher incidence of malignancies among people with HIV (PWH), despite the widespread use of antiretroviral therapy (ART), suggests a more complex relation than HIV-associated immune deregulation. Viral cooperation can have synergistic effect on tumorigenesis. The most relevant oncogenes involved in viral cooperation include the HIV-1-related Tat and Vpu genes, EBV LMP-1 and EBNA-2 genes, and Kaposi's sarcoma herpesvirus (KSHV) KIE2, Rta, and LANA genes. The TME in HIV-related malignancies is highly angiogenic and characterized by high microvessel density compared to sporadic cases. Tat protein, found in patients with HIV infection regardless of their immune status, has been widely implicated in the increased angiogenesis and has been a target of interest for therapeutic strategies. Similarly, HIV-1 matrix protein p17 can be detected in the plasma and tissues of PWH, including those treated with ART. Studies have found that p17 can cause dysregulation of the biological activity of different immune cells, is involved in aberrant angiogenesis, and exhibits an IL8 chemokine activity, activating multiple intracellular signaling pathways, promoting angiogenic responses in endothelial cells, and forming capillary like structures. In addition, several studies have demonstrated difference in the cellular immune components within the TME in patients with or without HIV infection, as well as cases in pre- and post-ART era. In this chapter, we review the existing literature about the role tumor microenvironment plays in the pathogenesis of HIV-related malignancies. Understanding the functions of each component of the TME and determining how these cellular and noncellular components contribute to tumorigenesis will impact the advancement of interventions and treatment in clinical oncology among PWH.

Primary central nervous system lymphoma in patients with and without HIV infection: a multicenter study and comparison with U.S national data.

PURPOSE: Primary central nervous system lymphoma (PCNSL) in patients living with HIV (PLWH) is a distinct entity; however, the management is adopted from patients without HIV. The study aims to examine the differences in presentation, treatment, and outcomes of PCNSL patients with or without HIV. METHODS: We retrospectively compared the characteristics of 144 patients with PCNSL with and without HIV, and analyzed factors associated with overall and progression-free survival. Results were compared to the Central Brain Tumor Registry of the United States (CBTRUS) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) system. RESULTS: Among all patients with PCNSL, 19% had HIV. PLWH were younger (38 vs. 63 years; p < 0.01) and more likely to be African American (59% vs. 7%; p < 0.01) and male (74% vs. 49%; p = 0.02) than patients without HIV. PLWH were more likely to have multiple lesions (67% vs. 43%; p = 0.02), hemorrhage (59 vs. 37%; p = 0.03), and peripheral rim enhancement (57% vs. 7%; p < 0.01) on imaging; to receive palliative care (15% vs. 2%) or whole brain radiation (63% vs. 3%); and less likely to receive chemotherapy (22% vs. 95%) (p < 0.01). Twenty-four patients, none PLWH, underwent stem cell transplant. Not receiving transplant was an independent factor in mortality and disease progression. Our cohort of patients, compared to the national database, were younger (60 vs. 65 years), 58% were white vs. 75%, and had longer median overall survival 43 vs. 25 months. CONCLUSION: Epidemiology, imaging, and treatment options for patients with PCNSL with and without HIV differ, but HIV was not an independent factor of mortality or disease progression. More efforts are needed to improve access to research and treatment options for PLWH with PCNSL.

IMAGING LOCALIZATION AND SURGICAL APPROACH IN THE MANAGEMENT OF ECTOPIC PARATHYROID ADENOMAS.

OBJECTIVE: ( 1) Review the anatomy and epidemiology of ectopic parathyroid adenomas (EPAs), ( 2) summarize the role of relevant imaging modalities in the localization of EPAs, and ( 3) characterize surgical approaches for various ectopic locations. METHODS: Literature review of published English-language articles from 1995 through August 2017. RESULTS: Summary of the literature indicates that the prevalence of EPA is approximately 20% in unexplored patients with primary hyperparathyroidism, but it is as high as 66% in re-operative patients. EPAs may be located anywhere from the carotid bifurcation to the aorto-pulmonary window. Ultrasound has limited accuracy in identifying EPAs except near the thyroid and thyrothymic ligament and requires expert experience from the user. Among dual-phase 99mTc sestamibi scintigraphy techniques, hybrid imaging with both single-photon emission computed tomography (SPECT) and computed tomography (CT) (SPECT/CT) is superior to planar scintigraphy or SPECT alone at localizing EPAs. Four-dimensional computed tomography (4DCT) precisely delineates important anatomic relationships and is highly sensitive in localizing EPAs. Although 4DCT requires radiation, intravenous iodinated contrast, and reader experience, it is well-equipped to detect lesions at various ectopic sites and guide the surgical approach. EPAs frequently require alternative surgical approaches. Re-operative parathyroidectomy may be attempted in patients having previously undergone bilateral neck exploration by an experienced surgeon once the lesion is colocalized by 2 repeat imaging modalities. Removal of nonlocalized disease requires a careful and systematic exploration of superior and inferior gland locations. CONCLUSION: EPAs pose challenges during both localization and surgical removal. High-volume experience and multidisciplinary care are necessary for optimal outcomes. ABBREVIATIONS: CT = computed tomography; 4DCT = 4-dimensional CT; EPA = ectopic parathyroid adenoma; EPG = ectopic parathyroid gland; PHPT = primary hyperparathyroidism; RLN = recurrent laryngeal nerve; SPECT = single-photon emission computed tomography; TE = tracheo-esophageal.

Spinal cord watershed infarction after surgery.

Spinal cord watershed infarction is a rare phenomenon due to the rich collateral blood supply to the organ. It often occurs in elderly patients with preexisting atherosclerotic disease in the setting of global hypoperfusion, such as thoracoabdominal surgery, dissection, coagulopathies, or idiopathic. We present a case of spinal cord infarction (SCI) in both longitudinal and transverse watershed areas as a complication of postoperative blood loss. In addition, we demonstrate the imaging evolution of spinal cord infarct in the subacute phase with peripheral enhancement due to the breakdown of the blood-spinal cord barrier.

Robust AI-Driven Segmentation of Glioblastoma T1c and FLAIR MRI Series and the Low Variability of the MRIMath© Smart Manual Contouring Platform.

Patients diagnosed with glioblastoma multiforme (GBM) continue to face a dire prognosis. Developing accurate and efficient contouring methods is crucial, as they can significantly advance both clinical practice and research. This study evaluates the AI models developed by MRIMath© for GBM T1c and fluid attenuation inversion recovery (FLAIR) images by comparing their contours to those of three neuro-radiologists using a smart manual contouring platform. The mean overall Sørensen-Dice Similarity Coefficient metric score (DSC) for the post-contrast T1 (T1c) AI was 95%, with a 95% confidence interval (CI) of 93% to 96%, closely aligning with the radiologists' scores. For true positive T1c images, AI segmentation achieved a mean DSC of 81% compared to radiologists' ranging from 80% to 86%. Sensitivity and specificity for T1c AI were 91.6% and 97.5%, respectively. The FLAIR AI exhibited a mean DSC of 90% with a 95% CI interval of 87% to 92%, comparable to the radiologists' scores. It also achieved a mean DSC of 78% for true positive FLAIR slices versus radiologists' scores of 75% to 83% and recorded a median sensitivity and specificity of 92.1% and 96.1%, respectively. The T1C and FLAIR AI models produced mean Hausdorff distances (<5 mm), volume measurements, kappa scores, and Bland-Altman differences that align closely with those measured by radiologists. Moreover, the inter-user variability between radiologists using the smart manual contouring platform was under 5% for T1c and under 10% for FLAIR images. These results underscore the MRIMath© platform's low inter-user variability and the high accuracy of its T1c and FLAIR AI models.

Anti-Ma2 Encephalitis: An Atypical Case Associated With Klüver-Bucy Syndrome and Hypothalamic Dysfunction.

Anti-Ma2 encephalitis is a rare form of autoimmune encephalitis that has classically been described as a paraneoplastic neurobehavioral disorder due to its association with underlying malignancies. We discuss the case of a 30-year-old female with an exceptionally aggressive presentation of anti-Ma2 encephalitis accompanied by Klüver-Bucy syndrome and hypothalamic dysfunction. Her course was complicated by repeated aspiration events secondary to severe hyperphagia and delays in immunosuppressive treatment due to concerns of infection. The patient's encephalitis was refractory to multiple immunosuppressive therapies and she ultimately expired before a primary malignancy could be detected and treated.

Evaluation of RANO Criteria for the Assessment of Tumor Progression for Lower-Grade Gliomas.

PURPOSE: The Response Assessment in Neuro-Oncology (RANO) criteria for lower-grade gliomas (LGGs) define tumor progression as ≥25% change in the T2/FLAIR signal area based on an operator's discretion of the perpendicular diameter of the largest tumor cross-section. Potential sources of error include acquisition inconsistency of 2D slices, operator selection variabilities in both representative tumor cross-section and measurement line locations, and the inability to quantify infiltrative tumor margins and satellite lesions. Our goal was to assess the accuracy and reproducibility of RANO in LG. MATERIALS AND METHODS: A total of 651 FLAIR MRIs from 63 participants with LGGs were retrospectively analyzed by three blinded attending physicians and three blinded resident trainees using RANO criteria, 2D visual assessment, and computer-assisted 3D volumetric assessment. RESULTS: RANO product measurements had poor-to-moderate inter-operator reproducibility (r2 = 0.28-0.82; coefficient of variance (CV) = 44-110%; mean percent difference (diff) = 0.4-46.8%) and moderate-to-excellent intra-operator reproducibility (r2 = 0.71-0.88; CV = 31-58%; diff = 0.3-23.9%). When compared to 2D visual ground truth, the accuracy of RANO compared to previous and baseline scans was 66.7% and 65.1%, with an area under the ROC curve (AUC) of 0.67 and 0.66, respectively. When comparing to volumetric ground truth, the accuracy of RANO compared to previous and baseline scans was 21.0% and 56.5%, with an AUC of 0.39 and 0.55, respectively. The median time delay at diagnosis was greater for false negative cases than for false positive cases for the RANO assessment compared to previous (2.05 > 0.50 years, p = 0.003) and baseline scans (1.08 > 0.50 years, p = 0.02). CONCLUSION: RANO-based assessment of LGGs has moderate reproducibility and poor accuracy when compared to either visual or volumetric ground truths.

Osseous Manifestations of Primary Hyperparathyroidism: Imaging Findings.

Primary hyperparathyroidism is a systemic endocrine disease that has significant effects on bone remodeling through the action of parathyroid hormone on the musculoskeletal system. These findings are important as they can aid in distinguishing primary hyperparathyroidism from other forms of metabolic bone diseases and inform physicians regarding disease severity and complications. This pictorial essay compiles bone-imaging features with the aim of improving the diagnosis of skeletal involvement of primary hyperthyroidism.

Localization of Parathyroid Disease in Reoperative Patients with Primary Hyperparathyroidism.

The localization of persistent or recurrent disease in reoperative patients with primary hyperparathyroidism presents challenges for radiologists and surgeons alike. In this article, we summarize the relevant imaging modalities, compare their accuracy in identifying reoperative disease, and outline their advantages and disadvantages. Accurate localization by preoperative imaging is a predictor of operative success, whereas negative or discordant preoperative imaging is a risk factor for operative failure. Ultrasound is a common first-line modality because it is inexpensive, accessible, and radiation-free. However, it is highly operator-dependent and less accurate in the reoperative setting than in the primary setting. Sestamibi scintigraphy is superior to ultrasound in localizing reoperative disease but requires radiation, prolonged imaging times, and reader experience for accurate interpretation. Like ultrasound, sestamibi scintigraphy is less accurate in the reoperative setting because reoperative patients can exhibit distorted anatomy, altered perfusion of remaining glands, and interference of radiotracer uptake. Meanwhile, four-dimensional computed tomography (4DCT) is superior to ultrasound and sestamibi scintigraphy in localizing reoperative disease but requires the use of radiation and intravenous contrast. Both 4DCT and magnetic resonance imaging (MRI) do not significantly differ in accuracy between unexplored and reoperative patients. However, MRI is more costly, inaccessible, and time-consuming than 4DCT and is inappropriate as a first-line modality. Hybrid imaging with positron emission tomography and computed tomography (PET/CT) may be a promising second-line modality in the reoperative setting, particularly when first-line modalities are discordant or inconclusive. Lastly, selective venous sampling should be reserved for challenging cases in which noninvasive modalities are negative or discordant. In the challenging population of reoperative patients with PHPT, a multimodality approach that utilizes the expertise of high-volume centers can accurately localize persistent or recurrent disease and enable curative parathyroidectomy.

Histogram analysis of apparent diffusion coefficient and fluid-attenuated inversion recovery in discriminating between enhancing and nonenhancing lesions in multiple sclerosis.

PURPOSE: This study evaluates the diagnostic performance of apparent diffusion coefficient (ADC) and T2 fluid-attenuation inversion recovery (T2 FLAIR) in discriminating between new white matter (WM) enhancing lesions (ELs) and non-enhancing lesions (NELs) in multiple sclerosis (MS) patients. METHODS: Thirty MS patients with a new solitary WM lesion on brain MRI were analyzed. A region-of-interest was drawn on all lesions and the contralateral normal-appearing WM (NAWM) on T2 FLAIR and ADC maps. Normalized ratios of T2 FLAIR and ADC were calculated by dividing lesion value by the contralateral NAWM. Histogram analysis was performed on the T2 FLAIR, ADC values, and their normalized ratios. Mann-Whitney U test was used to compare histogram parameters and receiver operating characteristic (ROC) analysis determined the area under the curve (AUC). RESULTS: T2 FLAIR histogram parameters were not significantly different between ELs and NELs. Several EL ADC histogram parameters, including maximum and mean, were significantly higher than NELs (p = 0.006 to p = 0.031). There was a trend toward significantly higher maximum ADC in ELs after adjusting for multiple comparisons (p = 0.054). The standard deviation of T2 FLAIR (AUC 0.70), maximum ADC (AUC 0.79), and normalized maximum ADC ratio (AUC 0.75) were among histogram parameters with the highest diagnostic performance. A maximum ADC cutoff of 1274 × 10-6 mm2/s provided a 0.86 sensitivity and 0.75 specificity. CONCLUSION: In patients with contraindications to gadolinium or concerns with gadolinium brain deposition, consideration may be given to ADC and T2 FLAIR as potential noncontrast methods for the evaluation of active MS lesions.

Diffusion-weighted MR imaging histogram analysis in HIV positive and negative patients with primary central nervous system lymphoma as a predictor of outcome and tumor proliferation.

INTRODUCTION: Ki-67 expression, a marker of tumor proliferation, is considered a prognostic factor in primary CNS lymphoma (PCNSL). Apparent diffusion coefficient (ADC) parameters have also been proposed as imaging biomarkers for tumor progression and proliferative activity in various malignancies. The aim of this study is to investigate the correlation between ADC parameters, Ki-67 expression, overall survival (OS) and progression free survival (PFS) in PCNSL. MATERIALS AND METHODS: Patients diagnosed with PCNSL at MD Anderson Cancer Center between Mar 2000 and Jul 2016 and at Ben Taub Hospital between Jan 2012 and Dec 2016 were retrospectively studied. Co-registered ADC maps and post-contrast images underwent whole tumor segmentation. Normalized ADC parameters (nADC) were calculated as the ratio to normal white matter. Percentiles of nADC were calculated and were correlated with Ki-67 using Pearson's correlation coefficient and clinical outcomes (OS and PFS) using Cox proportional hazards models. RESULTS: Selection criteria yielded 90 patients, 23 patients living with HIV (PLWH) and 67 immunocompetent patients. Above median values for nADCmean, nADC15, nADC75 and nADC95 were associated with improved OS in all patients (p < 0.05). Above median values for nADCmin, nADCmean, nADC1, nADC5 and kurtosis were associated with improved PFS in all patients (p < 0.05). In patients with available Ki-67 expression data (n = 22), nADCmean, nADC15 and nADC75 inversely correlated with Ki-67 expression (p < 0.05). For PLWH, there was no correlation between ADC parameters and Ki-67 expression or clinical outcomes. CONCLUSIONS: ADC histogram analysis can predict tumor proliferation and survival in immunocompetent patients with PCNSL, but with limited utility in PLWH.

Construction of a Machine Learning Dataset through Collaboration: The RSNA 2019 Brain CT Hemorrhage Challenge.

This dataset is composed of annotations of the five hemorrhage subtypes (subarachnoid, intraventricular, subdural, epidural, and intraparenchymal hemorrhage) typically encountered at brain CT.

Erratum: Construction of a Machine Learning Dataset through Collaboration: The RSNA 2019 Brain CT Hemorrhage Challenge.

[This corrects the article DOI: 10.1148/ryai.2020190211.].

Whole Tumor Histogram Analysis Using DW MRI in Primary Central Nervous System Lymphoma Correlates with Tumor Biomarkers and Outcome.

The ability to non-invasively predict outcomes and monitor treatment response in primary central nervous system lymphoma (PCNSL) is important as treatment regimens are constantly being trialed. The aim of this study was to assess the validity of using apparent diffusion coefficient (ADC) histogram values to predict Ki-67 expression, a tumor proliferation marker, and patient outcomes in PCNSL in both immunocompetent patients and patients living with HIV (PLWH). Qualitative PCNSL magnetic resonance imaging (MRI) characteristics from 93 patients (23 PLWH and 70 immunocompetent) were analyzed, and whole tumor segmentation was performed on the ADC maps. Quantitative histogram analyses of the segmentations were calculated. These measures were compared to PCNSL Ki-67 expression. Progression-free survival (PFS) and overall survival (OS) were analyzed via comparison to the International Primary Central Nervous System Lymphoma Collaboration Group Response Criteria. Associations between ADC measures and clinical outcomes were assessed using univariate and multivariate Cox proportional hazards models. Normalized ADC (nADC)Min, nADCMean, nADC1, nADC5, and nADC15 values were significantly associated with a poorer OS. nADCMax, nADCMean, nADC5, nADC15, nADC75, nADC95, nADC99 inversely correlated with Ki-67 expression. OS was also significantly associated with lesion hemorrhage. PFS was not significantly associated with ADC values but with lesion hemorrhage. ADC histogram values and related parameters can predict the degree of tumor proliferation and patient outcomes for primary central nervous system lymphoma patients and in both immunocompetent patients and patients living with HIV.

Multicenter study demonstrates radiomic features derived from magnetic resonance perfusion images identify pseudoprogression in glioblastoma.

Pseudoprogression (PsP) is a diagnostic clinical dilemma in cancer. In this study, we retrospectively analyse glioblastoma patients, and using their dynamic susceptibility contrast and dynamic contrast-enhanced perfusion MRI images we build a classifier using radiomic features obtained from both Ktrans and rCBV maps coupled with support vector machines. We achieve an accuracy of 90.82% (area under the curve (AUC) = 89.10%, sensitivity = 91.36%, 67 specificity = 88.24%, p = 0.017) in differentiating between pseudoprogression (PsP) and progressive disease (PD). The diagnostic performances of the models built using radiomic features from Ktrans and rCBV separately were equally high (Ktrans: AUC = 94%, 69 p = 0.012; rCBV: AUC = 89.8%, p = 0.004). Thus, this MR perfusion-based radiomic model demonstrates high accuracy, sensitivity and specificity in discriminating PsP from PD, thus provides a reliable alternative for noninvasive identification of PsP versus PD at the time of clinical/radiologic question. This study also illustrates the successful application of radiomic analysis as an advanced processing step on different MR perfusion maps.

Primary extradural paraganglioma of the thoracic spine: A case report.

Paragangliomas are rare, mostly benign neuroendocrine tumors arising from autonomic paraganglia. Spinal paragangliomas are uncommon, and among these, paragangliomas of the thoracic spine are distinctly unusual. We present the case of a primary paraganglioma of the extradural thoracic spine in a 34-year-old woman.

Single phase computed tomography is equivalent to dual phase method for localizing hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism: a retrospective review.

OBJECTIVE: This study aims to compare the sensitivity of dual phase (non-contrast and arterial) versus single phase (arterial) CT for detection of hyper-functioning parathyroid glands in patients with primary hyperparathyroidism. METHODS: The CT scans of thirty-two patients who have biochemical evidence of primary hyperparathyroidism, pathologically proven parathyroid adenomas, and pre-operative multiphase parathyroid imaging were evaluated retrospectively in order to compare the adequacy of single phase vs. dual phase CT scans for the detection of parathyroid adenomas. RESULTS: The parathyroid adenomas were localized in 83% of cases on single arterial phase CT and 80% of cases on dual phase CT. The specificity for localization of parathyroid tumor was 96% for single phase CT and 97% for dual phase CT. The results were not significantly different (p = 0.695). These results are similar to those found in the literature for multiphase CT of 55-94%. CONCLUSIONS: Our study supports the use of a single arterial phase CT for the detection of hyperfunctioning parathyroid adenomas. Advances in knowledge: a single arterial phase CT has similar sensitivity for localizing parathyroid adenomas as dual phase CT and significantly reduces radiation dose to the patient.

Spontaneous thrombosis of a traumatic posterior cerebral artery aneurysm in a child.

Traumatic posterior circulation aneurysms are rare, especially in children. They are typically associated with severe trauma and are thought to result from either direct osseous injury or stretching or compression of an artery against the tentorium. They may grow, rupture, or both. Although spontaneous thrombosis may occur, it rarely results in complete occlusion. We report the spontaneous and complete thrombosis of a large posterior cerebral artery aneurysm in a child who presented after minor head trauma. Five-year follow-up documents the complete occlusion of the aneurysm.

Endovascular treatment of high-flow carotid cavernous fistulas by stent-assisted coil placement.

BACKGROUND AND PURPOSE: Endovascular techniques are the methods of choice for the treatment of patients with carotid cavernous fistulas. We report our experience using stent-assisted coil placement for treatment of patients with high-flow fistulas that are associated with severe laceration of the internal carotid artery. METHODS: In a retrospective review of an internal endovascular therapy database covering the interval between October 2001 and October 2003, we identified a total of 5 patients presenting with 6 high-flow type A carotid cavernous fistulas (one had a bilateral fistula) that were associated with severe laceration of the internal carotid artery. All were treated first with stenting of the injured segment of the internal carotid artery followed by transarterial (3/6) and/or transvenous (4/6) obliteration of the fistula with detachable platinum coils. In 2 cases, a liquid adhesive was also used. In all instances, a compliant balloon was inflated within the stented arterial segment during coil deposition to avoid extension of coils into the parent artery. RESULTS: All 6 fistulas were obliterated, and each internal carotid artery was successfully reconstructed. Except for posttraumatic cranial nerve dysfunction in 1 patient, clinical outcome was very good. Follow-up angiograms in 3 of the 6 patients obtained at intervals between 3 and 6 months (mean, 4.5 months) revealed no fistula recurrence and no evidence of intimal hyperplasia within the stent. CONCLUSION: In this series of patients with high-flow carotid cavernous fistula associated with severe injury to the internal carotid artery, stent-assisted coil placement offered a safe and effective treatment. Stent-assisted coil placement may increase the ability to successfully treat fistulas with severe injury to the internal carotid artery with preservation of the parent artery.

Lumps and bumps on the head in children: use of CT and MR imaging in solving the clinical diagnostic dilemma.

Lumps and bumps of the scalp are a common presenting complaint in children and often pose a diagnostic dilemma. These lesions can be difficult to image, with evaluation confounded by their small size. However, accuracy in diagnosis is critical because the diagnostic and therapeutic implications can vary significantly. The clinical examination can be helpful in developing the differential diagnosis and the imaging strategy. Often, however, a single imaging study is insufficient, and the radiologist finds it necessary to image with more than one modality to correctly diagnose a lesion and provide adequate information for the surgeon. Radiography and ultrasonography are often the initial screening diagnostic tests, followed by magnetic resonance (MR) imaging or computed tomography (CT) for more detail. Multidetector thin-section CT and thin-section MR imaging with surface coils are beneficial in the work-up of these small lesions of the head and neck. The use of newer MR imaging sequences such as heavily T2-weighted single-shot turbo spin-echo imaging and diffusion-weighted imaging can improve the characterization of difficult lesions. Familiarity with the variety of new imaging tools and techniques that are available can help characterize pediatric head and neck lesions and guide clinical management.