Cytotoxic lesions of the corpus callosum: a systematic review.

OBJECTIVES: Cytotoxic lesions of the corpus callosum (CLOCC) are a common magnetic resonance imaging (MRI) finding associated with various systemic diseases including COVID-19. Although an increasing number of such cases is reported in the literature, there is a lack of systematic evidence summarizing the etiology and neuroimaging findings of these lesions. Thus, the aim of this systematic review was to synthesize the applied nomenclature, neuroimaging and clinical features, and differential diagnoses as well as associated disease entities of CLOCC. MATERIALS AND METHODS: A comprehensive literature search in three biomedical databases identified 441 references, out of which 324 were eligible for a narrative summary including a total of 1353 patients. RESULTS: Our PRISMA-conform systematic review identifies a broad panel of disease entities which are associated with CLOCC, among them toxic/drug-treatment-associated, infectious (viral, bacterial), vascular, metabolic, traumatic, and neoplastic entities in both adult and pediatric individuals. On MRI, CLOCC show typical high T2 signal, low T1 signal, restricted diffusion, and lack of contrast enhancement. The majority of the lesions were reversible within the follow-up period (median follow-up 3 weeks). Interestingly, even though CLOCC were mostly associated with symptoms of the underlying disease, in exceptional cases, CLOCC were associated with callosal neurological symptoms. Of note, employed nomenclature for CLOCC was highly inconsistent. CONCLUSIONS: Our study provides high-level evidence for clinical and imaging features of CLOCC as well as associated disease entities. CLINICAL RELEVANCE STATEMENT: Our study provides high-level evidence on MRI features of CLOCC as well as a comprehensive list of disease entities potentially associated with CLOCC. Together, this will facilitate rigorous diagnostic workup of suspected CLOCC cases. KEY POINTS: • Cytotoxic lesions of the corpus callosum (CLOCC) are a frequent MRI feature associated with various systemic diseases. • Cytotoxic lesions of the corpus callosum show a highly homogenous MRI presentation and temporal dynamics. • This comprehensive overview will benefit (neuro)radiologists during diagnostic workup.

Multiparametric magnetic resonance imaging discerns glioblastoma immune microenvironmental heterogeneity.

RATIONALE AND OBJECTIVE: Poor clinical outcomes for patients with glioblastoma are in part due to dysfunction of the tumor-immune microenvironment. An imaging approach able to characterize immune microenvironmental signatures could provide a framework for biologically based patient stratification and response assessment. We hypothesized spatially distinct gene expression networks can be distinguished by multiparametric Magnetic Resonance Imaging (MRI) phenotypes. MATERIALS AND METHODS: Patients with newly diagnosed glioblastoma underwent image-guided tissue sampling allowing for co-registration of MRI metrics with gene expression profiles. MRI phenotypes based on gadolinium contrast enhancing lesion (CEL) and non-enhancing lesion (NCEL) regions were subdivided based on imaging parameters (relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC)). Gene set enrichment analysis and immune cell type abundance was estimated using CIBERSORT methodology. Significance thresholds were set at a p-value cutoff 0.005 and an FDR q-value cutoff of 0.1. RESULTS: Thirteen patients (eight men, five women, mean age 58 ± 11 years) provided 30 tissue samples (16 CEL and 14 NCEL). Six non-neoplastic gliosis samples differentiated astrocyte repair from tumor associated gene expression. MRI phenotypes displayed extensive transcriptional variance reflecting biological networks, including multiple immune pathways. CEL regions demonstrated higher immunologic signature expression than NCEL, while NCEL regions demonstrated stronger immune signature expression levels than gliotic non-tumor brain. Incorporation of rCBV and ADC metrics identified sample clusters with differing immune microenvironmental signatures. CONCLUSION: Taken together, our study demonstrates that MRI phenotypes provide an approach for non-invasively characterizing tumoral and immune microenvironmental glioblastoma gene expression networks.

Syndromic vascular malformations related to the PIK3CA and RAS pathways: A clinical and imaging review.

Vascular malformations are a complex and diverse group of disorders. They may enlarge with time, impair quality of life, and even be fatal. While many are sporadic, others are part of inherited syndromes; several gene mutations responsible for vascular anomalies have been identified. The PI3K/AKT/mTOR and RAS/MEK/ERK cascades have been extensively studied, and new molecular agents targeting these cascades are being developed. Diagnostic imaging findings are increasingly used to guide genetic testing, and in some cases, pathognomonic imaging characteristics can lead to a specific diagnosis. We review each of the representative syndromes associated with PIK3CA and RAS cascades, with updates of the latest in clinical and imaging information.

Diagnostic reference levels and median doses for common clinical indications of CT: findings from an international registry.

OB JECTIVES: The European Society of Radiology identified 10 common indications for computed tomography (CT) as part of the European Study on Clinical Diagnostic Reference Levels (DRLs, EUCLID), to help standardize radiation doses. The objective of this study is to generate DRLs and median doses for these indications using data from the UCSF CT International Dose Registry. METHODS: Standardized data on 3.7 million CTs in adults were collected between 2016 and 2019 from 161 institutions across seven countries (United States of America (US), Switzerland, Netherlands, Germany, UK, Israel, Japan). DRLs (75th percentile) and median doses for volumetric CT-dose index (CTDIvol) and dose-length product (DLP) were assessed for each EUCLID category (chronic sinusitis, stroke, cervical spine trauma, coronary calcium scoring, lung cancer, pulmonary embolism, coronary CT angiography, hepatocellular carcinoma (HCC), colic/abdominal pain, appendicitis), and US radiation doses were compared with European. RESULTS: The number of CT scans within EUCLID categories ranged from 8,933 (HCC) to over 1.2 million (stroke). There was greater variation in dose between categories than within categories (p < .001), and doses were significantly different between categories within anatomic areas. DRLs and median doses were assessed for all categories. DRLs were higher in the US for 9 of the 10 indications (except chronic sinusitis) than in Europe but with a significantly higher sample size in the US. CONCLUSIONS: DRLs for CTDIvol and DLP for EUCLID clinical indications from diverse organizations were established and can contribute to dose optimization. These values were usually significantly higher in the US than in Europe. KEY POINTS: • Registry data were used to create benchmarks for 10 common indications for CT identified by the European Society of Radiology. • Observed US radiation doses were higher than European for 9 of 10 indications (except chronic sinusitis). • The presented diagnostic reference levels and median doses highlight potentially unnecessary variation in radiation dose.

Comparison of the Effectiveness of Single-Component and Multicomponent Interventions for Reducing Radiation Doses in Patients Undergoing Computed Tomography: A Randomized Clinical Trial.

Importance: Computed tomography (CT) radiation doses vary across institutions and are often higher than needed. Objective: To assess the effectiveness of 2 interventions to reduce radiation doses in patients undergoing CT. Design, Setting, and Participants: This randomized clinical trial included 864 080 adults older than 18 years who underwent CT of the abdomen, chest, combined abdomen and chest, or head at 100 facilities in 6 countries from November 1, 2015, to September 21, 2017. Data analysis was performed from October 4, 2017, to December 14, 2018. Interventions: Imaging facilities received audit feedback alone comparing radiation-dose metrics with those of other facilities followed by the multicomponent intervention, including audit feedback with targeted suggestions, a 7-week quality improvement collaborative, and best-practice sharing. Facilities were randomly allocated to the time crossing from usual care to the intervention. Main Outcomes and Measures: Primary outcomes were the proportion of high-dose CT scans and mean effective dose at the facility level. Secondary outcomes were organ doses. Outcomes after interventions were compared with those before interventions using hierarchical generalized linear models adjusting for temporal trends and patient characteristics. Results: Across 100 facilities, 864 080 adults underwent 1 156 657 CT scans. The multicomponent intervention significantly reduced proportions of high-dose CT scans, measured using effective dose. Absolute changes in proportions of high-dose scans were 1.1% to 7.9%, with percentage reductions in the proportion of high-dose scans of 4% to 30% (abdomen: odds ratio [OR], 0.82; 95% CI, 0.77-0.88; P < .001; chest: OR, 0.92; 95% CI, 0.86-0.99; P = .03; combined abdomen and chest: OR, 0.49; 95% CI, 0.41-0.59; P < .001; and head: OR, 0.71; 95% CI, 0.66-0.76; P < .001). Reductions in the proportions of high-dose scans were greater when measured using organ doses. The absolute reduction in the proportion of high-dose scans was 6.0% to 17.2%, reflecting 23% to 58% reductions in the proportions of high-dose scans across anatomical areas. Mean effective doses were significantly reduced after multicomponent intervention for abdomen (6% reduction, P < .001), chest (4%, P < .001), and chest and abdomen (14%, P < .001) CT scans. Larger reductions in mean organ doses were 8% to 43% across anatomical areas. Audit feedback alone reduced the proportions of high-dose scans and mean dose, but reductions in observed dose were smaller. Radiologist's satisfaction with CT image quality was unchanged and high during all periods. Conclusions and Relevance: For imaging facilities, detailed feedback on CT radiation dose combined with actionable suggestions and quality improvement education significantly reduced doses, particularly organ doses. Effects of audit feedback alone were modest. Trial Registration: ClinicalTrials.gov Identifier: NCT03000751.

Diagnostic performance and inter-operator variability of apparent diffusion coefficient analysis for differentiating pleomorphic adenoma and carcinoma ex pleomorphic adenoma: comparing one-point measurement and whole-tumor measurement including radiomics approach.

BACKGROUND AND PURPOSE: The purpose of this study was to compare the diagnostic performance between apparent diffusion coefficient (ADC) analysis of one-point measurement and whole-tumor measurement, including radiomics for differentiating pleomorphic adenoma (PA) from carcinoma ex pleomorphic adenoma (CXPA), and to evaluate the impact of inter-operator segmentation variability. MATERIALS AND METHODS: One hundred and fifteen patients with PA and 22 with CXPA were included. Four radiologists with different experience independently placed one-point and whole-tumor ROIs and a radiomics-predictive model was constructed from the extracted imaging features. We calculated the area under the receiver-operator characteristic curve (AUC) for the diagnostic performance of imaging features and the radiomics-predictive model. RESULTS: AUCs of the imaging features from whole-tumor varied between readers (0.50-0.89). The most experienced radiologist (Reader 1) produced significantly high AUCs than less experienced radiologists (Reader 3 and 4; P = 0.01 and 0.009). AUCs were higher for the radiomics-predictive model (0.82-0.87) than for one-point (0.66-0.79) in all readers. CONCLUSION: Some imaging features of whole-tumor and radiomics-predictive model had higher diagnostic performance than one-point. The diagnostic performance of imaging features from whole-tumor alone varied depending on operator experience. Operator experience appears less likely to affect diagnostic performance in the radiomics-predictive model.

International variation in radiation dose for computed tomography examinations: prospective cohort study.

OBJECTIVE: To determine patient, institution, and machine characteristics that contribute to variation in radiation doses used for computed tomography (CT). DESIGN: Prospective cohort study. SETTING: Data were assembled and analyzed from the University of California San Francisco CT International Dose Registry. PARTICIPANTS: Standardized data from over 2.0 million CT examinations of adults who underwent CT between November 2015 and August 2017 from 151 institutions, across seven countries (Switzerland, Netherlands, Germany, United Kingdom, United States, Israel, and Japan). MAIN OUTCOME MEASURES: Mean effective doses and proportions of high dose examinations for abdomen, chest, combined chest and abdomen, and head CT were determined by patient characteristics (sex, age, and size), type of institution (trauma center, care provision 24 hours per day and seven days per week, academic, private), institutional practice volume, machine factors (manufacturer, model), country, and how scanners were used, before and after adjustment for patient characteristics, using hierarchical linear and logistic regression. High dose examinations were defined as CT scans with doses above the 75th percentile defined during a baseline period. RESULTS: The mean effective dose and proportion of high dose examinations varied substantially across institutions. The doses varied modestly (10-30%) by type of institution and machine characteristics after adjusting for patient characteristics. By contrast, even after adjusting for patient characteristics, wide variations in radiation doses across countries persisted, with a fourfold range in mean effective dose for abdomen CT examinations (7.0-25.7 mSv) and a 17-fold range in proportion of high dose examinations (4-69%). Similar variation across countries was observed for chest (mean effective dose 1.7-6.4 mSv, proportion of high dose examinations 1-26%) and combined chest and abdomen CT (10.0-37.9 mSv, 2-78%). Doses for head CT varied less (1.4-1.9 mSv, 8-27%). In multivariable models, the dose variation across countries was primarily attributable to institutional decisions regarding technical parameters (that is, how the scanners were used). CONCLUSIONS: CT protocols and radiation doses vary greatly across countries and are primarily attributable to local choices regarding technical parameters, rather than patient, institution, or machine characteristics. These findings suggest that the optimization of doses to a consistent standard should be possible. STUDY REGISTRATION: Clinicaltrials.gov NCT03000751.

MR imaging findings in some rare neurological complications of paediatric cancer.

Neurological complications of paediatric cancers are a substantial problem. Complications can be primary from central nervous system (CNS) spread or secondary from indirect or remote effects of cancer, as well as cancer treatments such as chemotherapy and radiation therapy. In this review, we present the clinical and imaging findings of rare but important neurological complications in paediatric patients with cancer. Neurological complications are classified into three phases: pre-treatment, treatment and post-remission. Paraneoplastic neurological syndromes, hyperviscosity syndrome, haemophagocytic lymphohistiocytosis and infection are found in the pre-treatment phase, while Trousseau's syndrome, posterior reversible encephalopathy syndrome and methotrexate neurotoxicity are found in the treatment phase; though some complications overlap between the pre-treatment and treatment phases. Hippocampal sclerosis, radiation induced tumour, radiation induced focal haemosiderin deposition and radiation-induced white matter injury are found in the post-remission phase. With increasingly long survival after treatment, CNS complications have become more common. It is critical for radiologists to recognise neurological complications related to paediatric cancer or treatment. Magnetic resonance imaging (MRI) plays a significant role in the recognition and proper management of the neurological complications of paediatric cancer. TEACHING POINTS: • Neurological complications of paediatric cancer include various entities. • Neurological complications are classified into three phases: pre-treatment, treatment and post-remission. • Radiologists should be familiar with clinical and imaging findings of neurological complications. • MRI features may be characteristic and lead to early diagnosis and proper treatments.

Cytotoxic Lesions of the Corpus Callosum That Show Restricted Diffusion: Mechanisms, Causes, and Manifestations.

Cytotoxic lesions of the corpus callosum (CLOCCs) are secondary lesions associated with various entities. CLOCCs have been found in association with drug therapy, malignancy, infection, subarachnoid hemorrhage, metabolic disorders, trauma, and other entities. In all of these conditions, cell-cytokine interactions lead to markedly increased levels of cytokines and extracellular glutamate. Ultimately, this cascade can lead to dysfunction of the callosal neurons and microglia. Cytotoxic edema develops as water becomes trapped in these cells. On diffusion-weighted magnetic resonance (MR) images, CLOCCs manifest as areas of low diffusion. CLOCCs lack enhancement on contrast material-enhanced images, tend to be midline, and are relatively symmetric. The involvement of the corpus callosum typically shows one of three patterns: (a) a small round or oval lesion located in the center of the splenium, (b) a lesion centered in the splenium but extending through the callosal fibers laterally into the adjacent white matter, or (c) a lesion centered posteriorly but extending into the anterior corpus callosum. CLOCCs are frequently but not invariably reversible. Their pathologic mechanisms are discussed, the typical MR imaging findings are described, and typical cases of CLOCCs are presented. Although CLOCCs are nonspecific with regard to the underlying cause, additional imaging findings and the clinical findings can aid in making a specific diagnosis. Radiologists should be familiar with the imaging appearance of CLOCCs to avoid a misdiagnosis of ischemia. When CLOCCs are found, the underlying cause of the lesion should be sought and addressed. ©RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on February 13, 2017.

Predicting Retear after Repair of Full-Thickness Rotator Cuff Tear: Two-Point Dixon MR Imaging Quantification of Fatty Muscle Degeneration-Initial Experience with 1-year Follow-up.

Purpose To determine the degree of preoperative fatty degeneration within muscles, postoperative longitudinal changes in fatty degeneration, and differences in fatty degeneration between patients with full-thickness supraspinatus tears who do and those who do not experience a retear after surgery. Materials and Methods This prospective study had institutional review board approval and was conducted in accordance with the Committee for Human Research. Informed consent was obtained. Fifty patients with full-thickness supraspinatus tears (18 men, 32 women; mean age, 67.0 years ± 8.0; age range, 41-91 years) were recruited. The degrees of preoperative and postoperative fatty degeneration were quantified by using a two-point Dixon magnetic resonance (MR) imaging sequence; two radiologists measured the mean signal intensity on in-phase [S(In)] and fat [S(Fat)] images. Estimates of fatty degeneration were calculated with "fat fraction" values by using the formula S(Fat)/S(In) within the supraspinatus, infraspinatus, and subscapularis muscles at baseline preoperative and at postoperative 1-year follow-up MR imaging. Preoperative fat fractions in the failed-repair group and the intact-repair group were compared by using the Mann-Whitney U test. Results The preoperative fat fractions in the supraspinatus muscle were significantly higher in the failed-repair group than in the intact-repair group (37.0% vs 19.5%, P < .001). Fatty degeneration of the supraspinatus muscle tended to progress at 1 year postoperatively in only the failed-repair group. Conclusion MR imaging quantification of preoperative fat fractions by using a two-point Dixon sequence within the rotator cuff muscles may be a viable method for predicting postoperative retear. (©) RSNA, 2016.

Human papillomavirus-associated plantar epidermoid cysts: MR and US imaging appearance.

Epidermoid cysts are epithelial cysts that present as slow-growing intradermal or subcutaneous lesions. While recent epidemiological studies have isolated human papillomavirus (HPV) from plantar epidermoid cysts, imaging findings in HPV-associated epidermoid cysts have not been previously reported. We describe imaging findings in two patients with HPV-associated plantar epidermoid cysts. Magnetic resonance (MR) imaging and ultrasonography (US) showed linear arrangement of several adjacent globular cysts. This appearance is hypothesized to result from HPV-associated eccrine duct metaplasia leading to cyst formation and later traumatic rupture leading to formation of multiple adjacent cystic components. It may be useful to suggest assessing the presence of HPV antigen in plantar lesions having these imaging findings.

Why are autopsy rates low in Japan? Views of ordinary citizens and doctors in the case of unexpected patient death and medical error.

This article examines what could account for the low autopsy rate in Japan based on the findings from an anonymous, self-administered, structured questionnaire that was given to a sample population of the general public and physicians in Japan. The general public and physicians indicated that autopsy may not be carried out because: (1) conducting an autopsy might result in the accusation that patient death was caused by a medical error even when there was no error (50.4% vs. 13.1%, respectively), (2) suggesting an autopsy makes the families suspicious of a medical error even when there was none (61.0% vs. 19.1%, respectively), (3) families do not want the body to be damaged by autopsy (81.6% vs. 87.3%, respectively), and (4) families do not want to make the patient suffer any more in addition to what he/she has already endured (61.8% vs. 87.1%, respectively).

Responsibility for reporting patient death due to hospital error in Japan when an error occurred at a referring institution.

In Japan, physicians are required to report unexpected health care-associated patient deaths to the police. Patients needing to be transferred to another institution often have complex medical problems. If a medical error occurs, it may be either at the final or the referring institution. Some fear that liability will fall on the final institution regardless of where the error occurred or that the referring facility may oppose such reporting, leading to a failure to report to police or to recommend an autopsy. Little is known about the actual opinions of physicians and risk managers in this regard. The authors sent standardised, self-administered questionnaires to all hospitals in Japan that participate in the national general residency program. Most physicians and risk managers in Japan indicated that they would report a patient's death to the police where the patient has been transferred. Of those who indicated they would not report to the police, the majority still indicated they would recommend an autopsy

Attitudes toward clinical autopsy in unexpected patient deaths in Japan: a nation-wide survey of the general public and physicians.

CONTEXT: Autopsy is a useful tool for understanding the cause and manner of unexpected patient death. However, the attitudes of the general public and physicians in Japan about clinical autopsy are limited. OBJECTIVE: To describe the beliefs of the general public about whether autopsy should be performed and ascertain if they would actually request one given specific clinical situations where patient death occurred with the additional variable of medical error. To compare these attitudes with previously obtained attitudes of physicians practising at Japanese teaching hospitals. DESIGN, SETTING AND PARTICIPANTS: We conducted a cross-sectional study of the general public. We sent standardised questionnaires in 2010 to a randomly selected non-physician adult population using a survey company for participant selection. Respondents gave their opinions about the necessity of autopsy and how they might act given various clinical scenarios of patient death. We compared these results with those of a previous survey of Japanese physicians conducted in 2009. RESULTS: Of the 2300 eligible general adult population, 1575 (68.5%) responded. The majority of the general public indicated they believed an autopsy was necessary. However, in cases of unclear medical error or unclear cause and effect relationship of medical care and patient death, the general public were much less likely to indicate they would actually request an autopsy than were physicians (p<0.0001). Currently in Japan the debate about the role autopsy should play in the case of error related to death is underway. The results from this study will be important in informing related decisions.

Patient safety education at Japanese medical schools: results of a nationwide survey.

BACKGROUND: Patient safety education, including error prevention strategies and management of adverse events, has become a topic of worldwide concern. The importance of the patient safety is also recognized in Japan following two serious medical accidents in 1999. Furthermore, educational curriculum guideline revisions in 2008 by relevant the Ministry of Education includes patient safety as part of the core medical curriculum. However, little is known about the patient safety education in Japanese medical schools partly because a comprehensive study has not yet been conducted in this field. Therefore, we have conducted a nationwide survey in order to clarify the current status of patient safety education at medical schools in Japan. RESULTS: Response rate was 60.0% (n = 48/80). Ninety-eight-percent of respondents (n = 47/48) reported integration of patient safety education into their curricula. Thirty-nine percent reported devoting less than five hours to the topic. All schools that teach patient safety reported use of lecture based teaching methods while few used alternative methods, such as role-playing or in-hospital training. Topics related to medical error theory and legal ramifications of error are widely taught while practical topics related to error analysis such as root cause analysis are less often covered. CONCLUSIONS: Based on responses to our survey, most Japanese medical schools have incorporated the topic of patient safety into their curricula. However, the number of hours devoted to the patient safety education is far from the sufficient level with forty percent of medical schools that devote five hours or less to it. In addition, most medical schools employ only the lecture based learning, lacking diversity in teaching methods. Although most medical schools cover basic error theory, error analysis is taught at fewer schools. We still need to make improvements to our medical safety curricula. We believe that this study has the implications for the rest of the world as a model of what is possible and a sounding board for what topics might be important.

A pictorial review of benign hepatocellular nodular lesions: comprehensive radiological assessment incorporating the concept of anomalous portal tract syndrome.

BACKGROUND/PURPOSE: Although the pathological categorization system advocated by the International Working Party (IWP) on Terminology has been helpful in categorizing benign hepatocellular lesions, the diverse clinicopathological features of the lesions still cause confusion of diagnosis in clinical settings. Recently, an integrated disease concept termed "anomalous portal tract syndrome" (APTS) has been proposed as a congenital anomaly of the portal tract, being a single unifying etiological factor underlying the disorder. In this article, we discuss the radiological features of benign nodular hepatocellular lesions incorporated in the concept of APTS. METHODS: We systematically reviewed the literature on benign hepatocellular lesions based on the concept of APTS, as well as standard IWP terminology. For this pictorial review, we selected six representative cases and assessed the radiological features of the cases based on the concept of APTS. RESULTS: The comprehensive assessment based on APTS enabled the systematic categorization of benign hepatocellular lesions, including nodular regenerative hyperplasia, large regenerative nodules, partial nodular transformation, focal nodular hyperplasia, and hepatocellular adenoma, and was helpful in understanding the overlapping features of these lesions. CONCLUSIONS: Although the disease concept of APTS is still evolving, it is nonetheless helpful in comprehensively understanding the clinicopathological and radiological features of various benign hepatocellular lesions.