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A woman presented at age 18 years with partial myelitis and diplopia and experienced multiple subsequent relapses. Her MRI demonstrated T2 abnormalities characteristic of multiple sclerosis (MS) (white matter ovoid lesions and Dawson fingers), and CSF demonstrated an elevated IgG index and oligoclonal bands restricted to the CSF. Diagnosed with clinically definite relapsing-remitting MS, she was treated with various MS disease-modifying therapies and eventually began experiencing secondary progression. At age 57 years, she developed an acute longitudinally extensive transverse myelitis and was found to have AQP4 antibodies by cell-based assay. Our analysis of the clinical course, radiographic findings, molecular diagnostic methods, and treatment response characteristics support the hypothesis that our patient most likely had 2 CNS inflammatory disorders: MS, which manifested as a teenager, and neuromyelitis optica spectrum disorder, which evolved in her sixth decade of life. This case emphasizes a key principle in neurology practice, which is to reconsider whether the original working diagnosis remains tenable, especially when confronted with evidence (clinical and/or paraclinical) that raises the possibility of a distinctively different disorder., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Maxillofacial trauma patients comprise a significant subset of patients presenting to emergency departments. Before evaluating for facial trauma, an emergency or trauma physician must perform a primary survey to ensure patient stabilization. Following this primary survey, this document discusses the following clinical scenarios for facial trauma: tenderness to palpation or contusion or edema over frontal bone (suspected frontal bone injury); pain with upper jaw manipulation or pain overlying zygoma or zygomatic deformity or facial elongation or malocclusion or infraorbital nerve paresthesia (suspected midface injury); visible nasal deformity or palpable nasal deformity or tenderness to palpation of the nose or epistaxis (suspected nasal bone injury); and trismus or malocclusion or gingival hemorrhage or mucosal hemorrhage or loose teeth or fractured teeth or displaced teeth (suspected mandibular injury). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: T2/FLAIR hyperintensity of the optic nerve/optic nerve head has been described as a sensitive finding in idiopathic intracranial hypertension using post-contrast 3D-T2/FLAIR imaging. The purpose of this study is to assess whether hyperintensity on non-enhanced 2D-T2/FLAIR imaging occurs more likely in diseased patients than controls and to evaluate the relationship between FLAIR signal and visual parameters MATERIALS AND METHODS: A retrospective case-control study was performed of patients with idiopathic intracranial hypertension and controls who underwent orbital MRI. Three neuroradiologists reviewed the FLAIR images, subjectively evaluating for hyperintense signal within the optic nerves/optic nerve heads using a 5-point Likert Scale. Quantitative assessment of optic nerve signal using regions of interests was performed. Clinical parameters were extracted. The diagnostic performance was evaluated, and Spearman correlation calculated to assess the relationship between FLAIR signal and visual outcomes., Results: The sensitivity of abnormal FLAIR signal within the optic nerves and optic nerve heads in patients with idiopathic intracranial hypertension ranged from 25-54% and 4-29%, respectively, with specificities ranging from 67-92% and 83-100%. Quantitative assessment revealed a significant difference in CNR between cases and controls in the left posterior optic nerve (p=.002). A positive linear relationship existed between abnormal optic nerve head signal and papilledema grade (OD: p=.02, OS: p=.008) but not with other visual parameters., Conclusion: T2/FLAIR hyperintensity in the optic nerve/optic nerve head may support the diagnosis of idiopathic intracranial hypertension but its absence should not dissuade it. If present, abnormal signal in the optic nerve head correlates with papilledema., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

In the United States, acute low back pain, with or without radiculopathy, is the leading cause of years lived with disability and the third ranking cause of disability-adjusted life-years. Uncomplicated acute low back pain and/or radiculopathy is a benign, self-limited condition that does not warrant any imaging studies. Imaging is considered in those patients who have had up to 6 weeks of medical management and physical therapy that resulted in little or no improvement in their back pain. It is also considered for those patients presenting with red flags, raising suspicion for a serious underlying condition, such as cauda equina syndrome, malignancy, fracture, or infection. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Spine infection is both a clinical and diagnostic imaging challenge due to its relatively indolent and nonspecific clinical presentation. The diagnosis of spine infection is based upon a combination of clinical suspicion, imaging evaluation and, when possible, microbiologic confirmation performed from blood cultures or image-guided percutaneous or open spine biopsy. With respect to the imaging evaluation of suspected spine infection, MRI without and with contrast of the affected spine segment is the initial diagnostic test of choice. As noncontrast MRI of the spine is often used in the evaluation of back or neck pain not responding to conservative medical management, it may show findings that are suggestive of infection, hence this procedure may also be considered in the evaluation of suspected spine infection. Nuclear medicine studies, including skeletal scintigraphy, gallium scan, and FDG-PET/CT, may be helpful in equivocal or select cases. Similarly, radiography and CT may be appropriate for assessing overall spinal stability, spine alignment, osseous integrity and, when present, the status of spine instrumentation or spine implants. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Hyperparathyroidism is defined as excessive parathyroid hormone production. The diagnosis is made through biochemical testing, in which imaging has no role. However, imaging is appropriate for preoperative parathyroid gland localization with the intent of surgical cure. Imaging is particularly useful in the setting of primary hyperparathyroidism whereby accurate localization of a single parathyroid adenoma can facilitate minimally invasive parathyroidectomy. Imaging can also be useful to localize ectopic or supernumerary parathyroid glands and detail anatomy, which may impact surgery. This document summarizes the literature and provides imaging recommendations for hyperparathyroidism including primary hyperparathyroidism, recurrent or persistent primary hyperparathyroidism after parathyroid surgery, secondary hyperparathyroidism, and tertiary hyperparathyroidism. Recommendations include ultrasound, CT neck without and with contrast, and nuclear medicine parathyroid scans. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Plexopathy may be caused by diverse pathologies, including trauma, nerve entrapment, neoplasm, inflammation, infection, autoimmune disease, hereditary disease, and idiopathic etiologies. For patients presenting with brachial or lumbosacral plexopathy, dedicated plexus MRI is the most appropriate initial imaging modality for all clinical scenarios and can identify processes both intrinsic and extrinsic to the nerves. Other imaging tests may be appropriate for initial imaging depending on the clinical scenario. This document addresses initial imaging strategies for brachial and lumbosacral plexopathy in the following clinical situations: nontraumatic plexopathy with no known malignancy, traumatic plexopathy (not perinatal), and plexopathy occurring in the context of a known malignancy or posttreatment syndrome. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: HIV-1 infections occur following viral exposure at anogenital mucosal surfaces in the presence of semen. Semen contains immunosuppressive and pro-inflammatory factors. Semen from HIV-1-infected donors contains anti-HIV-1 antibodies. We assessed if passively infused anti-HIV-1 neutralizing antibody conferred protection from rectal SHIV SF162P3 challenge at semen exposed mucosae., Methods: We pooled seminal plasma from HIV-1-infected donors. The pool was screened by ELISA for antibodies against HIV-1 SF162 gp140. The ability of seminal plasma to inhibit macaque NK cells from responding to direct and antibody-dependent stimulation was assessed. The ability of seminal plasma to inhibit macaque granulocytes from mediating oxidative burst was also assessed. To demonstrate viral infectivity in the presence of seminal plasma, macaques (n = 4) were rectally challenged with SHIV SF162P3 following exposure to 2.5 mL of seminal plasma. To evaluate if anti-HIV-1 neutralizing antibody confers protection against rectal SHIV challenge at semen exposed mucosae, eight macaques were intravenously infused with PGT121, either wild type (n = 4) or the Fc receptor binding deficient LALA variant (n = 4), and rectally challenged with SHIV SF162P3 following exposure to 2.5 mL of seminal plasma., Findings: Anti-HIV-1 SF162 gp140 antibodies were detected in seminal plasma. Seminal plasma inhibited direct and antibody-dependent NK cell activation and granulocyte oxidative burst in vitro. Rectal SHIV SF162P3 challenge of control macaques following seminal plasma exposure resulted in infection of all animals. All macaques infused with wild type or LALA PGT121 and challenged with SHIV SF162P3 following seminal plasma exposure were protected., Interpretation: PGT121 conferred protection against rectal SHIV SF162P3 challenge at semen exposed mucosae. Future research should investigate if semen alters protection conferred by antibodies more dependent on non-neutralizing functions., Funding: This work was supported by a grant from the Australian National Health and Medical Research Council (APP1124680)., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Visualization of annular fissures on MRI is becoming increasingly important but remains challenging. Our purpose was to test whether an image processing algorithm could improve detection of annular fissures., Materials and Methods: In this retrospective study, two neuroradiologists identified 56 IVDs with annular fissures and 97 IVDs with normal annulus fibrosus in lumbar spine MRIs of 101 patients (58 M, 43 F; age ± SD 15.1 ± 3.0 years). Signal intensities of diseased and normal annulus fibrosus, and contrast-to-noise ratio between them on sagittal T2-weighted images were calculated before and after processing with a proprietary software. Effect of processing on detection of annular fissures by two masked neuroradiologists was also studied for IVDs with Pfirrmann grades of ≤ 2 and > 2., Results: Mean (SD) signal baseline intensities of diseased and normal annulus fibrosus were 57.6 (23.3) and 24.4 (7.8), respectively (p < 0.001). Processing increased (p < 0.001) the mean (SD) intensity of diseased annulus to 110.6 (47.9), without affecting the signal intensity of normal annulus (p = 0.14). Mean (SD) CNR between the diseased and normal annulus increased (p < 0.001) from 11.8 (14.1) to 29.6 (29.1). Both masked readers detected more annular fissures after processing in IVDs with Pfirrmann grade of ≤ 2 and > 2, with an apparent increased sensitivity and decreased specificity using predefined image-based human categorization as a reference standard., Conclusions: Image processing improved CNR of annular fissures and detection rate of annular fissures. However, further studies with a more stringent reference standard are needed to assess its effect on sensitivity and specificity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Myelopathy is a clinical diagnosis with localization of the neurological findings to the spinal cord, rather than the brain or the peripheral nervous system, and then to a particular segment of the spinal cord. Myelopathy can be the result of primary intrinsic disorders of the spinal cord or from secondary conditions, which result in extrinsic compression of the spinal cord. While the causes of myelopathy may be multiple, the acuity of presentation and symptom onset frame a practical approach to the differential diagnosis. Imaging plays a crucial role in the evaluation of myelopathy with MRI the preferred modality. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19 + B cells approximates 40%-50% of baseline levels as measured before alemtuzumab treatment inception), can mitigate alemtuzumab-associated secondary autoimmunity., Methods: In this hypothesis-driven pilot study, 10 patients received low-dose rituximab (50-150 mg/m 2 ), a chimeric anti-CD20 monoclonal antibody, after either their first or second cycles of alemtuzumab. These patients were then routinely assessed for the development of autoimmune disorders and safety signals related to the use of dual monoclonal antibody therapy., Results: Five patients received at least 1 IV infusion of low-dose rituximab, following alemtuzumab therapy, with a mean follow-up of 41 months. None of the 5 patients developed secondary autoimmune disorders. An additional 5 patients with follow-up over less than 24 months received at least 1 infusion of low-dose rituximab treatment following alemtuzumab treatment. No secondary autoimmune diseases were observed., Conclusions: An anti-CD20 "whack-a-mole" B-cell depletion strategy may serve to mitigate alemtuzumab-associated secondary autoimmunity in MS by reducing the imbalance in B- and T-cell regulatory networks during immune reconstitution. We believe that these observations warrant further investigation., Classification of Evidence: This study provides Class IV evidence that for people with MS, low-dose rituximab following alemtuzumab treatment decreases the risk of alemtuzumab-associated secondary autoimmune diseases., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Vδ2 + T cells play a critical role in immunity to micro-organisms and cancer but exhibit substantial heterogeneity in humans. Here, we demonstrate that CD26 and CD94 define transcriptionally, phenotypically, and functionally distinct Vδ2 + T cell subsets. Despite distinct antigen specificities, CD26 hi CD94 lo Vδ2 + cells exhibit substantial similarities to CD26 hi mucosal-associated invariant T (MAIT) cells, although CD26 - Vδ2 + cells exhibit cytotoxic, effector-like profiles. At birth, the Vδ2 + Vγ9 + population is dominated by CD26 hi CD94 lo cells; during adolescence and adulthood, Vδ2 + cells acquire CD94/NKG2A expression and the relative frequency of the CD26 hi CD94 lo subset declines. Critically, exposure of the CD26 hi CD94 lo subset to phosphoantigen in the context of interleukin-23 (IL-23) and CD26 engagement drives the acquisition of a cytotoxic program and concurrent loss of the MAIT cell-like phenotype. The ability to modulate the cytotoxic potential of CD26 hi CD94 lo Vδ2 + cells, combined with their adenosine-binding capacity, may make them ideal targets for immunotherapeutic expansion and adoptive transfer., Competing Interests: Declaration of Interests The authors declare no competing interests., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: Mesial temporal sclerosis (MTS) is an important cause of intractable epilepsy. Early and accurate diagnosis of MTS is essential to providing curative and life-changing therapy but can be challenging in children in whom the impact of diagnosis is particularly high. Magnetic resonance imaging (MRI) plays an important role in the diagnosis of MTS, and image processing of MRI is a recently studied strategy to improve its accuracy., Objective: In a retrospective case-control study, we assessed the performance of an image processing algorithm (Correlative Image Enhancement [CIE]) for detecting MTS-related hippocampal signal abnormality in children., Materials and Methods: Twenty-seven pediatric MTS cases (9 males, 18 females; mean age: 16±standard deviation [SD] 6.7 years) were identified from a pathology database of amygdylo-hippocampectomies performed in children with epilepsy. Twenty-seven children with no seizure history (9 males, 18 females; mean age: 13.8±SD 2.8 years), and with normal brain MRI, were identified for the control group. Blinded investigators processed the MRI coronal FLAIR (fluid-attenuated inversion recovery) images with CIE, saved the processed images as a separate series, and made equivalent region of interest measurements on the processed and unprocessed series to calculate contrast-to-noise ratio. Six blinded reviewers then rated the randomized series for hippocampal signal abnormality and MTS disease status., Results: CIE increased signal intensity and contrast-to-noise ratio in 26/27 hippocampi with pathologically confirmed MTS (96.3%) with the mean (SD) contrast-to-noise ratio of cases increasing from 14.9 (11.1) to 77.7 (58.7) after processing (P<0.001). Contrast-to-noise ratio increased in 1/54 normal control hippocampi (1.9%), with no significant change in the mean contrast-to-noise ratio of the control group after processing (P=0.57). Mean (SD) reader sensitivity for detecting abnormal signal intensity increased from 83.3% (14.2) to 94.8% (3.3) after processing. Mean specificity for abnormal signal intensity increased from 94.4% (7.3) to 96.3% (0). While sensitivity improved after processing for detection of MTS disease status in 4/6 readers, the mean reader sensitivity and specificity for MTS detection increased only minimally after processing, from 79.6% to 80.7% and from 95.7% to 96.3%, respectively., Conclusion: The CIE image processing algorithm selectively increased the contrast-to-noise ratio of hippocampi affected by MTS, improved reader performance in detecting MTS-related hippocampal signal abnormality and could have high impact on pediatric patients undergoing work-up for seizures.

Neuroendocrine dysfunction includes suspected hyper- and hypofunction of the pituitary gland. Causative lesions may include primary masses of the pituitary such as pituitary microadenomas and macroadenomas, as well as extrinsic masses, typically centered in the suprasellar cistern. Clinical syndromes related to hormonal dysfunction can be caused by excessive hormonal secretion or by inhibited secretion due to mass effect upon elements of the hypothalamic-pituitary axis. Additionally, complications such as hemorrhage may be seen in the setting of an underlying mass and can result in hormonal dysfunction. MRI with high-resolution protocols is the best first-line test to evaluate the sella turcica and parasellar region. CT provides complementary information regarding bony anatomy, and may be appropriate as a first-line test in certain instances, but it provides less detail and lesion characterization when compared to MRI. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2019 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

There are a wide variety of diseases that affect the thyroid gland ranging from hyperplastic to neoplastic, autoimmune, or inflammatory. They can present with functional abnormality or a palpable structural change. Imaging has a key role in diagnosing and characterizing the thyroid finding for management. Imaging is also essential in the management of thyroid cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2019 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Ataxia can result from an abnormality in the cerebellum, spinal cord, peripheral nerves, and/or vestibular system. Pathology involving the brain, such as infarct or hydrocephalus, can also present with ataxia as part of the symptom constitution, or result in symptoms that mimic ataxia. Clinical evaluation by history and careful neurological examination is important to help with lesion localization, and helps determine where imaging should be focused. In the setting of trauma with the area of suspicion in the brain, a head CT without intravenous contrast is the preferred initial imaging choice. If vascular injury is suspected, CTA of the neck can be helpful. When the area of suspicion is in the spine, CT or MRI of the spine can be considered to assess for bony or soft-tissue injury, respectively. In the setting of ataxia unrelated to recent trauma, MRI is the preferred imaging modality, tailored to assess the brain or spine depending on the area of suspected pathology. The use of intravenous contrast is generally helpful. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2019 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: To test whether an image-processing algorithm can aid in visualization of mesial temporal sclerosis on magnetic resonance imaging by selectively increasing contrast-to-noise ratio (CNR) between abnormal hippocampus and normal brain., Materials and Methods: In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, baseline coronal fluid-attenuated inversion recovery images of 18 adults (10 females, eight males; mean age 41.2 years) with proven mesial temporal sclerosis were processed using a custom algorithm to produce corresponding enhanced images. Average (Hmean) and maximum (Hmax) CNR for abnormal hippocampus were calculated relative to normal ipsilateral white matter. CNR values for normal gray matter (GM) were similarly calculated using ipsilateral cingulate gyrus as the internal control. To evaluate effect of image processing on visual conspicuity of hippocampal signal alteration, a neuroradiologist masked to the side of hippocampal abnormality rated signal intensity (SI) of hippocampi on baseline and enhanced images using a five-point scale (definitely abnormal to definitely normal). Differences in Hmean, Hmax, GM, and SI ratings for abnormal hippocampi on baseline and enhanced images were assessed for statistical significance., Results: Both Hmean and Hmax were significantly higher in enhanced images as compared to baseline images (p < 0.0001 for both). There was no significant difference in the GM between baseline and enhanced images (p = 0.9375). SI ratings showed a more confident identification of abnormality on enhanced images (p = 0.0001)., Conclusion: Image-processing resulted in increased CNR of abnormal hippocampus without affecting the CNR of normal gray matter. This selective increase in conspicuity of abnormal hippocampus was associated with more confident identification of hippocampal signal alteration., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: Detection of mesial temporal sclerosis (MTS) in children with epilepsy is important. We assessed whether an image-processing algorithm (Correlative Image Enhancement, CIE) could facilitate recognition of hippocampal signal abnormality in the presence of MTS by increasing contrast to noise ratio between affected hippocampus and normal gray matter., Patients and Methods: Baseline coronal FLAIR images from brain MRIs of 27 children with epilepsy who underwent hippocampal resection were processed using CIE. These included 19 hippocampi with biopsy proven MTS and 8 biopsy proven normal hippocampi resected in conjunction with hemispherotomy. We assessed the effect of processing on contrast to noise ratio (CNR) between hippocampus and normal insular gray matter, and on assessment of hippocampal signal abnormality by two masked neuroradiologists., Results: Processing resulted in a significant increase in mean CNR (from 3.9 ± 5.3 to 25.3 ± 25.8; P < 0.01) for hippocampi with MTS, with a substantial (>100%) increase from baseline seen in 15/19 (78.9%) cases. Baseline CNR of 1.7 ± 5.3 for normal hippocampi did not change significantly after processing (1.8 ± 5.3; P = 1.00). For one reader, baseline sensitivity (14/19; 73.6%) was unaffected but the specificity improved from 62.5% (5/8) to 100%. An increase in both sensitivity (from 73.6% to 78.9%) and specificity (from 62.5% to 75%) was seen for the second reader., Conclusion: By enhancing CNR for diseased hippocampi while leaving normal hippocampi relatively unaffected, CIE may improve the diagnostic accuracies of radiologists in detecting MTS-related signal alteration within the affected hippocampus., (Copyright © 2018 Elsevier B.V. All rights reserved.)

It is widely thought that generating broadly neutralizing anti-HIV antibodies (BnAbs) will protect humans against HIV, given promising data from in vitro experiments and in vivo macaque studies. The primary action of BnAbs is preventing cell-free virus from entering cells. Recent in vitro and macaque data suggest that BnAbs are less potent against cell-associated virus exposure. We speculate that BnAb-based suppression of HIV transmission, particularly if mediated by cell-cell transmission, may result in some exposed subjects carrying a form of latent (or 'occult') HIV infection. Such largely hidden HIV infections may subsequently reactivate when BnAb levels decline. This concept has implications for the achievement of long-term sterilizing immunity to HIV., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Visual loss can be the result of an abnormality anywhere along the visual pathway including the globe, optic nerve, optic chiasm, optic tract, thalamus, optic radiations or primary visual cortex. Appropriate imaging analysis of visual loss is facilitated by a compartmental approach that establishes a differential diagnosis on the basis of suspected lesion location and specific clinical features. CT and MRI are the primary imaging modalities used to evaluate patients with visual loss and are often complementary in evaluating these patients. One modality may be preferred over the other depending on the specific clinical scenario. Depending on the pattern of visual loss and differential diagnosis, imaging coverage may require targeted evaluation of the orbits and/or assessment of the brain. Contrast is preferred when masses and inflammatory processes are differential considerations. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

The role of antibody Fc-mediated effector functions in controlling or preventing infections by human immunodeficiency type 1 (HIV-1) and simian immunodeficiency (SIV) viruses has been recently highlighted in multiple studies. One of those effector functions, antibody-dependent cellular cytotoxicity (ADCC) was suggested as correlating with decreased HIV-1 acquisition risk in the recent Thai RV144 vaccine trial. RV144-elicited antibodies with potent ADCC activity were recently found to recognize HIV envelope (Env) epitopes exposed upon Env-CD4 interaction. However, HIV-1 efficiently limits the exposure of those epitopes by strongly downregulating CD4 by both Nef and Vpu accessory proteins, as well as indirectly preventing the accumulation of Env at the cell surface by Vpu-mediated BST-2 antagonism. These accessory proteins were thus proposed to play a critical role in decreasing the susceptibility of HIV-infected cells to elimination by ADCC. In this review we will summarize these recent findings and discuss the critical role that HIV-1 envelope glycoproteins conformation plays on ADCC responses, how these responses can be measured in the laboratory, the role of HIV-1-transmission on ADCC responses and how this knowledge can be used to develop new strategies aimed at targeting HIV-1-infected cells.

Recent evidence from HIV vaccine trials in humans and non-human primates suggests that nonneutralizing antibody functions, such as antibody-dependent cellular cytotoxicity (ADCC), are an important component of vaccine-mediated protection. Whether anti-HIV ADCC antibodies are present in seminal fluid, however, is not known. We assessed whether anti-HIV antibodies within seminal plasma mediate ADCC and activate natural killer (NK) cells. Using matched blood and seminal plasma samples, we detected anti-HIV IgG within samples from all 11 HIV-infected donors. Furthermore, anti-HIV antibodies within the seminal plasma triggered detectable ADCC in 9 of 11 donors and activated NK cells in 6 of 11 donors. The ability of seminal plasma-derived IgG to activate NK cells in an anti-HIV antibody-dependent manner was enhanced when IgG were enriched and other seminal plasma components were removed. These observations have relevance for understanding natural immunity to HIV infection and provide assistance with HIV vaccine design.

Unlabelled: Lifelong antiretroviral therapy (ART) for HIV-1 does not diminish the established latent reservoir. A possible cure approach is to reactivate the quiescent genome from latency and utilize immune responses to eliminate cells harboring reactivated HIV-1. It is not known whether antibodies within HIV-1-infected individuals can recognize and eliminate cells reactivated from latency through antibody-dependent cellular cytotoxicity (ADCC). We found that reactivation of HIV-1 expression in the latently infected ACH-2 cell line elicited antibody-mediated NK cell activation but did not result in antibody-mediated killing. The lack of CD4 expression on these HIV-1 envelope (Env)-expressing cells likely resulted in poor recognition of CD4-induced antibody epitopes on Env. To examine this further, cultured primary CD4(+) T cells from HIV-1(+) subjects were used as targets for ADCC. These ex vivo-expanded primary cells were modestly susceptible to ADCC mediated by autologous or heterologous HIV-1(+) serum antibodies. Importantly, ADCC mediated against these primary cells could be enhanced following incubation with a CD4-mimetic compound (JP-III-48) that exposes CD4-induced antibody epitopes on Env. Our studies suggest that with sufficient reactivation and expression of appropriate Env epitopes, primary HIV-1-infected cells can be targets for ADCC mediated by autologous serum antibodies and innate effector cells. The results of this study suggest that further investigation into the potential of ADCC to eliminate reactivated latently infected cells is warranted., Importance: An HIV-1 cure remains elusive due to the persistence of long-lived latently infected cells. An HIV-1 cure strategy, termed "shock and kill," aims to reactivate HIV-1 expression in latently infected cells and subsequently eliminate the reactivated cells through immune-mediated killing. While recent research efforts have focused on reversing HIV-1 latency, it remains unclear whether preexisting immune responses within HIV-1(+) individuals can efficiently eliminate the reactivated cells. HIV-1-specific antibodies can potentially eliminate cells reactivated from latency via Fc effector functions by recruiting innate immune cells. Our study highlights the potential role that antibody-dependent cellular cytotoxicity might play in antilatency cure approaches., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Objective: Targeting redundancy within MRI can improve its cost-effective utilization. We sought to quantify potential redundancy in our brain MRI protocols., Materials and Methods: In this retrospective review, we aggregated 207 consecutive adults who underwent brain MRI and reviewed their medical records to document clinical indication, core diagnostic information provided by MRI, and its clinical impact. Contributory imaging abnormalities constituted positive core diagnostic information whereas absence of imaging abnormalities constituted negative core diagnostic information. The senior author selected core sequences deemed sufficient for extraction of core diagnostic information. For validating core sequences selection, four readers assessed the relative ease of extracting core diagnostic information from the core sequences. Potential redundancy was calculated by comparing the average number of core sequences to the average number of sequences obtained., Results: Scanning had been performed using 9.4±2.8 sequences over 37.3±12.3 minutes. Core diagnostic information was deemed extractable from 2.1±1.1 core sequences, with an assumed scanning time of 8.6±4.8 minutes, reflecting a potential redundancy of 74.5%±19.1%. Potential redundancy was least in scans obtained for treatment planning (14.9%±25.7%) and highest in scans obtained for follow-up of benign diseases (81.4%±12.6%). In 97.4% of cases, all four readers considered core diagnostic information to be either easily extractable from core sequences or the ease to be equivalent to that from the entire study. With only one MRI lacking clinical impact (0.48%), overutilization did not seem to contribute to potential redundancy., Conclusion: High potential redundancy that can be targeted for more efficient scanner utilization exists in brain MRI protocols.

Objective: The objective of our study was to compare the cost-effectiveness of two approaches to using MRI for the evaluation of patients with hearing loss., Materials and Methods: We developed a decision tree to compare the cost-effectiveness of conventional MRI with that of a proposed two-tiered model in which an initial 3D T2-weighted imaging examination was used to determine the need for comprehensive MR scanning. Three radiologists independently and blindly reviewed the 3D T2-weighted images acquired as part of the comprehensive MR examinations of 256 patients with hearing loss to assess the diagnostic efficacy of the two-tiered approach. Costs were defined in terms of both the scanner utilization time for the imaging facility and the dollar amount for payers. Effectiveness was defined in terms of the ability to correctly detect the presence or absence of disease., Results: The conventional approach was less cost-effective, with a baseline incremental cost-effectiveness ratio (ICER) of 27,299 minutes of scanner utilization per unit increase in effectiveness. Assuming a 50% reduction in the reimbursement of the technical component from the current level by the Centers for Medicare & Medicaid Services, this result reflected an ICER of $258,664 per unit increase in effectiveness. The results of a sensitivity analysis showed the robustness of the cost-effectiveness of the two-tiered imaging approach in a variety of scenarios that reflect differences in scanning practices and possible differences in recall rates. The conventional imaging approach was absolutely dominated by the two-tiered approach in the scenarios created to reflect the expected range of prevalence of disease., Conclusion: A two-tiered approach to MRI provides a more cost-effective alternative to the current approach of using a comprehensive MRI examination without and with contrast material to evaluate patients with hearing loss.

Objective: The purpose of this study was to compare the diagnostic efficacy and cost implications of a proposed two-tiered approach to MRI in patients with headache., Materials and Methods: We identified 245 consecutive patients with headache using MRI studies performed at a tertiary care facility between October 2009 and July 2011. Three radiologists prospectively used FLAIR sequences from these MR studies to diagnose underlying abnormality or to identify the need for a comprehensive MRI study. We compared the diagnostic efficacy and the cost implications of such a two-tiered approach with those of conventional MRI from the perspectives of the payer, the patient, and the imaging facility., Results: The sensitivity and specificity for two-tiered (83.3% and 100%, respectively) and conventional (91% and 97.8%, respectively) MRI approaches were not significantly different. Assuming a 50% reduction in the payment for the initial limited MRI performed as a first step of the two-tiered approach, this approach would have resulted in 44.8% savings to the payer. A substantial reduction in the scanner utilization time from 4168 minutes to 1249 minutes for the two-tiered approach would have enabled increased throughput at the imaging facility. Although 27 (11%) patients would have been recalled for a comprehensive MRI study in the two-tiered approach, the average time spent in the scanner by each patient would have been less for the two-tiered approach (5.1 minutes vs 17.0 minutes)., Conclusion: A two-tiered approach to MRI can serve as a viable cost-effective alternative to the conventional approach.