Radiomics for differentiation of the posterior fossa pilocytic astrocytoma versus hemangioblastomas in adults. A pilot study.

PURPOSE: Both pilocytic astrocytoma (PA) and hemangioblastoma (HB) are common primary neoplasms of the posterior fossa with similar radiological manifestations. This study was conducted to evaluate the role of Radiomics in differentiating these two conditions in adults. MATERIALS AND METHODS: After a retrospective search of our institutional imaging archive, adult patients with a known diagnosis of PA or HB were included. We reviewed each patient's most recent preoperative brain magnetic resonance imaging (MRI). The solid enhancing nodule of each lesion on post-contrast T1 sequence was manually segmented. Multiple Radiomics features were then extracted from each nodule using the Pyradiomics library. Subsequently, the most predictive features were identified by feature selection models. Following this, different machine learning (ML) models were constructed based on these selected features to classify lesions as PA or HB. Finally, we evaluated the performance of each model by leave-one-out cross-validation. RESULTS: With inclusion and exclusion criteria, 34 enhancing PA nodules and 39 HB nodules were selected. A total of 115 features were extracted from each enhancing nodule. Twelve characteristics were detected as most predictive of histopathological diagnosis. Among various ML models, the neural network had the best performance in differentiating these two conditions with an AUC of 0.9 and an accuracy of 82%. CONCLUSIONS: In this retrospective study, Radiomics MRI techniques demonstrated high performance in distinguishing adult posterior fossa PA from HB. Future development of Radiomics models may advance presurgical diagnosis of these two conditions when added to routine clinical practice and thus improve patient management.

Imaging spectrum of amyloid-related imaging abnormalities associated with aducanumab immunotherapy.

Alzheimer's Disease (AD) is a leading cause of morbidity. Management of AD has traditionally been aimed at symptom relief rather than disease modification. Recently, AD research has begun to shift focus towards disease-modifying therapies that can alter the progression of AD. In this context, a class of immunotherapy agents known as monoclonal antibodies target diverse cerebral amyloid-beta (Aß) epitopes to inhibit disease progression. Aducanumab was authorized by the US Food and Drug Administration (FDA) to treat AD on June 7, 2021. Aducanumab has shown promising clinical and biomarker efficacy but is associated with amyloid-related imaging abnormalities (ARIA). Neuroradiologists play a critical role in diagnosing ARIA, necessitating familiarity with this condition. This pictorial review will appraise the radiologic presentation of ARIA in patients on aducanumab.

Clinical applications of diffusion-weighted sequence in brain imaging: beyond stroke.

Diffusion-weighted imaging (DWI) is a well-established MRI sequence for diagnosing early stroke and provides therapeutic implications. However, DWI yields pertinent information in various other brain pathologies and helps establish a specific diagnosis and management of other central nervous system disorders. Some of these conditions can present with acute changes in neurological status and mimic stroke. This review will focus briefly on diffusion imaging techniques, followed by a more comprehensive description of the utility of DWI in common neurological entities beyond stroke.

Current Status and Quality of Machine Learning-Based Radiomics Studies for Glioma Grading: A Systematic Review.

INTRODUCTION: Radiomics now has significant momentum in the era of precision medicine. Glioma is one of the pathologies that has been extensively evaluated by radiomics. However, this technique has not been incorporated into clinical practice. In this systematic review, we selected and reviewed the published studies about glioma grading by radiomics to evaluate this technique's feasibility and its challenges. MATERIAL AND METHODS: Using seven different search strings, we considered all published English manuscripts from 2015 to September 2020 in PubMed, Embase, and Scopus databases. After implementing the exclusion and inclusion criteria, the final papers were selected for the methodological quality assessment based on our in-house Modified Radiomics Standard Scoring (RQS) containing 43 items (minimum score of 0, maximum score of 44). Finally, we offered our opinion about the challenges and weaknesses of the selected papers. RESULTS: By our search, 1,177 manuscripts were found (485 in PubMed, 343 in Embase, and 349 in Scopus). After the implementation of inclusion and exclusion criteria, 18 papers remained for the final analysis by RQS. The total RQS score ranged from 26 (59% of maximum possible score) to 43 (97% of maximum possible score) with a mean of 33.5 (76% of maximum possible score). CONCLUSION: The current studies are promising but very heterogeneous in design with high variation in the radiomics software, the number of extracted features, the number of selected features, and machine learning models. All of the studies were retrospective in design; many are based on small datasets and/or suffer from class imbalance and lack of external validation data-sets.

Susceptibility-Weighted Imaging in Neurodegenerative Disorders: A Review.

As human life expectancy increases, there is an increased prevalence of neurodegenerative disorders and dementia. There are many ongoing research trials for early diagnosis and management of dementia, and neuroimaging is a critical part of such studies. However, conventional neuroimaging often fails to provide enough diagnostic findings in patients with neurodegenerative disorders. In this context, different MRI sequences are currently under investigation to facilitate the accurate diagnosis of such disorders. Susceptibility-weighted imaging (SWI) is an innovative MRI technique that utilizes "magnitude" and "phase" images to produce an image contrast that is sensitive for the detection of susceptibility differences of the tissues. As many neurodegenerative disorders are associated with accelerated iron deposition and/or microhemorrhages in different parts of the brain, SWI can be applied to detect these diagnostic clues. For instance, in cerebral amyloid angiopathy, SWI can demonstrate cortical microhemorrhages, which are predominantly in the frontal and parietal regions. Or in Parkinson disease, abnormal swallow-tail sign on high-resolution SWI is highly diagnostic. Also, SWI is a useful sequence to detect the low signal intensity of precentral cortices in patients with amyotrophic lateral sclerosis. Being familiar with SWI findings in neurodegenerative disorders is critical for an accurate diagnosis. In this paper, the authors review the technical parameters of SWI, physiologic, and pathologic iron deposition in the brain, and the role of SWI in the evaluation of neurodegenerative disorders in daily practice.

Brainstem Encephalitis. The Role of Imaging in Diagnosis.

Encephalitis is a relatively challenging rare condition caused by a diverse group of etiologies. Brainstem encephalitis/Rhombencephalitis (BE), which affects the cerebellum, pons, and medulla, is even less common and more challenging for diagnosis and treatment. At this time, there is scattered data about BE in the literature, mainly in the form of case reports and case series. In this manuscript, the imaging presentation of BE is reviewed with the help of case examples. Many imaging presentations are not pathognomonic for BE; however, in many cases, clinical presentation, the spatial distribution of lesions, and other associated radiological lesions can provide the radiologists and clinician the clues to an accurate diagnosis.

Comparison of the efficacy of Tegatard and Tegretol as a monotherapy in patients with focal seizure with or without secondary generalization.

BACKGROUND: Carbamazepine is a first line treatment for focal epilepsy. Tegretol and Tegatard are two trade name of Carbamazepine. Tegretol is produced by Novartis Pharmaceutical Company, Switzerland. Recently, Raha pharmaceutical Company in Iran has produced CBZ which trade named is Tegatard. Extended usage of Tegatard instead of Tegretol has economic benefits for Iranian families. In this clinical trial, we aimed to compare therapeutic efficacy and safety of Tegretol and Tegatard in patients suffering from focal seizures with or without secondary generalization. METHODS: 200 patients with provoked or non-provoked focal seizure with or without secondary generalization were screened and 180 patients were fulfilled the criteria to enter this double blinded clinical trial study. Patients were divided into two groups, the first group (A) received Tegretol and the second group (B) Tegatard. Carbamazepine (CBZ) was prescribed with doses 10-20 mg/kg every 12 hours by neurologists. The patients were visited after 1, 3 and 6 months and the side effects and lab data in patients were investigated. RESULTS: Patients were divided into two groups, 88 patients in group A (Tegretol) (50 males and 38 females) and 92 in group B (Tegatard) (51 males and 41 females). Mean age of patients was 35.39±11.17 years. There was no significant difference according to age and gender, Carbamazepine dosage, EEG recording, neuroimaging change and adverse effects of antiepileptic drug between two groups (P>0.05). Regarding the drug efficacy, in group A and B, 60 (68%) and 58 (63%) patients were seizure free after 6 month follow up; respectively. The differences between two groups were not statistically significant (P value =0.46). CONCLUSION: Tegatard is an effective drug with similar efficacy, similar side effects and cost-effectiveness compared with Tegretol and could be used widely when indicated.

Breast cancer diagnosis: Imaging techniques and biochemical markers.

Breast cancer is a complex disease which is found as the second cause of cancer-associated death among women. Accumulating of evidence indicated that various factors (i.e., gentical and envirmental factors) could be associated with initiation and progression of breast cancer. Diagnosis of breast cancer patients in early stages is one of important aspects of breast cancer treatment. Among of various diagnosis platforms, imaging techniques are main diagnosis approaches which could provide valuable data on patients with breast cancer. It has been showed that various imaging techniques such as mammography, magnetic resonance imaging (MRI), positron-emission tomography (PET), Computed tomography (CT), and single-photon emission computed tomography (SPECT) could be used for diagnosis and monitoring patients with breast cancer in various stages. Beside, imaging techniques, utilization of biochemical biomarkers such as proteins, DNAs, mRNAs, and microRNAs could be employed as new diagnosis and therapeutic tools for patients with breast cancer. Here, we summarized various imaging techniques and biochemical biomarkers could be utilized as diagnosis of patients with breast cancer. Moreover, we highlighted microRNAs and exosomes as new diagnosis and therapeutic biomarkers for monitoring patients with breast cancer.

Polymorphisms in CD14 Gene May Modify Soluble CD14 Levels and Represent Risk Factors for Multiple Sclerosis.

BACKGROUND: Besides the central role of the adaptive immune system, a disturbance of innate immune system is also suggested to be involved in the pathogenesis of multiple sclerosis (MS). CD14, a receptor upregulated in activated microglia, is known to be an essential mediator of inflammation in innate immune responses. Therefore, in this study we aimed to assess possible roles of CD14-159 and -260 gene polymorphisms in MS susceptibility and the effects of those polymorphisms to its protein producing capacity in Iranian population. METHODS: In this case control study, CD14-159 and -260 polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 200 MS patients and 200 healthy controls matched in age and gender. Serum levels of soluble CD14 (sCD14) was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: There were significant differences in genotype distribution of CD14-159 and -260 polymorphisms between patients and controls (P = 0.01, for-both). Mean serum level of sCD14 was significantly higher in MS patients than in control subjects (3340.30 ± 612.50 ng/ml vs 2353.73 ± 539.07 ng/ml; P < 0.01). CONCLUSION: In summary, we conclude that CD14-159 and -260 polymorphisms are associated with the risk of MS in Iranian population and affects CD14 promoter activity, thereby regulating CD14 expression. Furthermore, our study provides preliminary evidence for the activation of innate immunity in the pathogenesis of MS. In addition, the findings of the present study suggest serum level of sCD14 as candidate biomarker of MS severity.

Mannose-binding Lectin Mediated Complement Pathway in Autoimmune Neurological Disorders.

Multiple sclerosis (MS) is a complex, demyelinating disease of the central nervous system (CNS) with variable phenotypic presentations, while Guillain-Barre Syndrome (GBS) is the prototypic acute inflammatory disorder that affects the peripheral nervous system. Myasthenia gravis (MG) is a T cell dependent and antibody mediated autoimmune disease. Although it has been shown that complement plays a critical role in the pathogenesis of MS, GBS, and MG, the role of mannose-binding lectin (MBL) as a biomarker of immunopathogensis of these diseases and also its association with the severity of them have been poorly investigated. Therefore, in this study we aimed to measure plasma levels of MBL in patients with MS, GBS, and MG. In a case-control study, plasma was obtained from healthy controls (n=100) and also patients with MS (n=120), GBS (n=30), and MG (n=30). Plasma level measurement of MBL was performed using enzyme-linked immunosorbent assay (ELISA). The mean serum level of MBL was significantly different between groups of patients and healthy controls (p<0.001). We also found a positive correlation between plasma levels of MBL and severity scores of MS, MG, and GBS patients including: expanded disability status scale (EDSS) (r=+0.60 and p=<0.001), quantitative myasthenia gravis score (QMGS) (r=+0.56 and p=0.01), and GBS disability scale (GDS) (r=+0.37 and p=0.04). Taken together, our findings suggest that complement activation mediated by MBL contributes to the pathogenesis and also severity of MS, MG, and GBS. However, because the lectin pathway can be involved in several phases of the immune response, further evidence will be required to elucidate the underlying mechanism.

Polymorphism in Leptin and Leptin Receptor Genes May Modify Leptin Levels and Represent Risk Factors for Multiple Sclerosis.

BACKGROUND: Leptin, the product of the ob gene, can modulate the immune responses and also seems to regulate Th1/Th2 balance by promoting a shift from the Th2 to the Th1 inflammatory cytokine pathway. Therefore, in this study, we aimed to investigate the association between polymorphisms of leptin gene (LEP) and leptin receptor gene (LEPR) and susceptibility to multiple sclerosis (MS). In addition, we investigated the influence of these two common polymorphisms on plasma levels of leptin. METHODS: This case-control study was conducted on 232 MS patients and 204 control subjects. Serum level measurement of leptin was performed using enzyme-linked immunosorbent assay (ELISA). G-2548-A LEP polymorphism and 223A/G polymorphism of the LEPR were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: There was a significant difference in allele/genotype frequencies of LEP gene among MS patients and control subjects (p<0.01). The genotype frequencies of LEPR polymorphism were also significantly different between control subjects and MS patients (p=0.02). The mean serum level of leptin was significantly higher in MS patients as compared with the controls (p<0.01). CONCLUSION: Our study implicates a significant role of LEP and LEPR polymorphisms and also leptin levels in the risk of MS and its severity. Furthermore, our findings suggest LEP and LEPR polymorphisms as important predictors for increased serum leptin in Iranian MS patients. Although this study provides new clinically relevant information regarding genetic determinants modulating risk of MS, further investigations are necessary to understand better the mechanistic implications of these observations in the development of MS.

A Novel Approach to Discriminate Subgroups in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of central nervous system. Since different types of immune cells are involved in MS pathogenesis, in this study we aimed to evaluate serum levels of several immunological components including soluble CD4 (sCD4), sCD8, sCD163, and immunoglobulins as markers of activity of T-cells, macrophages, and B-cells in different types of MS. Serum levels of sCD4, sCD8, and sCD163 of patients with relapsing-remitting MS (RRMS, n=61), primary progressive MS (PRMS, n=31), secondary progressive MS (SPMS, n=31), clinical isolated syndrome (CIS, n=31) and neuromyelitis optica (NMO, n=31), and healthy controls (n=49) were measured using enzyme-linked immunosorbent assay (ELISA). Serum levels of Ig-G, Ig-M, and Ig-A were determined using nephelometric technique. Serum levels of sCD4, sCD8, sCD163, Ig-G, Ig-M, and Ig-A were significantly different in five groups of cases (p<0.05). Furthermore, application of stepwise method of discriminant analysis yielded 4 significant discriminant functions of classification due to the presence of six levels of categorical variables in the analysis. The most important function explained 85.5% of the total variance with the correlation value of 0.79. Taken together, our preliminary analysis suggests that although we found some functions to discriminate most of the patients, further studies will be required to individuate immunological markers characterizing the different type of MS including RRMS, PPMS, SPMS, CIS and NMO as proved by the data on sCD4, sCD163, Ig-M, and Ig-G in blood.