Advancing Pediatric Sarcomas through Radiomics: A Systematic Review and Prospective Assessment Using Radiomics Quality Score (RQS) and Methodological Radiomics Score (METRICS).

Pediatric sarcomas, rare malignancies of mesenchymal origin, pose diagnostic and therapeutic challenges. In this review, we explore the role of radiomics in reshaping our understanding of pediatric sarcomas, emphasizing methodological considerations and applications such as diagnostics and predictive modeling. A systematic review conducted up to November 2023 identified 72 papers on radiomics analysis in pediatric sarcoma from PubMed/MEDLINE, Web of Knowledge, and Scopus. Following inclusion and exclusion criteria, 10 reports were included in this review. The studies, predominantly retrospective, focus on Ewing sarcoma and osteosarcoma, utilizing diverse imaging modalities, including CT, MRI, PET/CT, and PET/MRI. Manual segmentation is common, with a median of 35 features extracted. Radiomics Quality Score (RQS) and Methodological Radiomics Score (METRICS) assessments reveal a consistent emphasis on non-radiomic features, validation criteria, and improved methodological rigor in recent publications. Diagnostic applications dominate, with innovative studies exploring prognostic and treatment response aspects. Challenges include feature heterogeneity and sample size variations. The evolving landscape underscores the need for standardized methodologies. Despite challenges, the diagnostic and predictive potential of radiomics in pediatric oncology is evident, paving the way for precision medicine advancements.

Accuracy of Radiomics in Predicting IDH Mutation Status in Diffuse Gliomas: A Bivariate Meta-Analysis.

Purpose To perform a systematic review and meta-analysis assessing the predictive accuracy of radiomics in the noninvasive determination of isocitrate dehydrogenase (IDH) status in grade 4 and lower-grade diffuse gliomas. Materials and Methods A systematic search was performed in the PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases for relevant articles published between January 1, 2010, and July 7, 2021. Pooled sensitivity and specificity across studies were estimated. Risk of bias was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2, and methods were evaluated using the radiomics quality score (RQS). Additional subgroup analyses were performed according to tumor grade, RQS, and number of sequences used (PROSPERO ID: CRD42021268958). Results Twenty-six studies that included 3280 patients were included for analysis. The pooled sensitivity and specificity of radiomics for the detection of IDH mutation were 79% (95% CI: 76, 83) and 80% (95% CI: 76, 83), respectively. Low RQS scores were found overall for the included works. Subgroup analyses showed lower false-positive rates in very low RQS studies (RQS < 6) (meta-regression, z = -1.9; P = .02) compared with adequate RQS studies. No substantial differences were found in pooled sensitivity and specificity for the pure grade 4 gliomas group compared with the all-grade gliomas group (81% and 86% vs 79% and 79%, respectively) and for studies using single versus multiple sequences (80% and 77% vs 79% and 82%, respectively). Conclusion The pooled data showed that radiomics achieved good accuracy performance in distinguishing IDH mutation status in patients with grade 4 and lower-grade diffuse gliomas. The overall methodologic quality (RQS) was low and introduced potential bias. Keywords: Neuro-Oncology, Radiomics, Integration, Application Domain, Glioblastoma, IDH Mutation, Radiomics Quality Scoring Supplemental material is available for this article. Published under a CC BY 4.0 license.

A first look into radiomics application in testicular imaging: A systematic review.

The aim of this systematic review was to evaluate the state of the art of radiomics in testicular imaging by assessing the quality of radiomic workflow using the Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). A systematic literature search was performed to find potentially relevant articles on the applications of radiomics in testicular imaging, and 6 final articles were extracted. The mean RQS was 11,33 ± 3,88 resulting in a percentage of 31,48% ± 10,78%. Regarding QUADAS-2 criteria, no relevant biases were found in the included papers in the patient selection, index test, reference standard criteria and flow-and-timing domain. In conclusion, despite the publication of promising studies, radiomic research on testicular imaging is in its very beginning and still hindered by methodological limitations, and the potential applications of radiomics for this field are still largely unexplored.

Delta-radiomics in cancer immunotherapy response prediction: A systematic review.

Background: The new immunotherapies have not only changed the oncological therapeutic approach but have also made it necessary to develop new imaging methods for assessing the response to treatment. Delta radiomics consists of the analysis of radiomic features variation between different medical images, usually before and after therapy. Purpose: This review aims to evaluate the role of delta radiomics in the immunotherapy response assessment. Methods: A systematic search was performed in PubMed, Scopus, and Web Of Science using "delta radiomics AND immunotherapy" as search terms. The included articles' methodological quality was measured using the Radiomics Quality Score (RQS) tool. Results: Thirteen articles were finally included in the systematic review. Overall, the RQS of the included studies ranged from 4 to 17, with a mean RQS total of 11,15 ± 4,18 with a corresponding percentage of 30.98 ± 11.61 %. Eleven articles out of 13 performed imaging at multiple time points. All the included articles performed feature reduction. No study carried out prospective validation, decision curve analysis, or cost-effectiveness analysis. Conclusions: Delta radiomics has been demonstrated useful in evaluating the response in oncologic patients undergoing immunotherapy. The overall quality was found law, due to the lack of prospective design and external validation. Thus, further efforts are needed to bring delta radiomics a step closer to clinical implementation.

Role of artificial intelligence in oncologic emergencies: a narrative review.

Oncologic emergencies are a wide spectrum of oncologic conditions caused directly by malignancies or their treatment. Oncologic emergencies may be classified according to the underlying physiopathology in metabolic, hematologic, and structural conditions. In the latter, radiologists have a pivotal role, through an accurate diagnosis useful to provide optimal patient care. Structural conditions may involve the central nervous system, thorax, or abdomen, and emergency radiologists have to know the characteristics imaging findings of each one of them. The number of oncologic emergencies is growing due to the increased incidence of malignancies in the general population and also to the improved survival of these patients thanks to the advances in cancer treatment. Artificial intelligence (AI) could be a solution to assist emergency radiologists with this rapidly increasing workload. To our knowledge, AI applications in the setting of the oncologic emergency are mostly underexplored, probably due to the relatively low number of oncologic emergencies and the difficulty in training algorithms. However, cancer emergencies are defined by the cause and not by a specific pattern of radiological symptoms and signs. Therefore, it can be expected that AI algorithms developed for the detection of these emergencies in the non-oncological field can be transferred to the clinical setting of oncologic emergency. In this review, a craniocaudal approach was followed and central nervous system, thoracic, and abdominal oncologic emergencies have been addressed regarding the AI applications reported in literature. Among the central nervous system emergencies, AI applications have been reported for brain herniation and spinal cord compression. In the thoracic district the addressed emergencies were pulmonary embolism, cardiac tamponade and pneumothorax. Pneumothorax was the most frequently described application for AI, to improve sensibility and to reduce the time-to-diagnosis. Finally, regarding abdominal emergencies, AI applications for abdominal hemorrhage, intestinal obstruction, intestinal perforation, and intestinal intussusception have been described.

Explainable AI in radiology: a white paper of the Italian Society of Medical and Interventional Radiology.

The term Explainable Artificial Intelligence (xAI) groups together the scientific body of knowledge developed while searching for methods to explain the inner logic behind the AI algorithm and the model inference based on knowledge-based interpretability. The xAI is now generally recognized as a core area of AI. A variety of xAI methods currently are available to researchers; nonetheless, the comprehensive classification of the xAI methods is still lacking. In addition, there is no consensus among the researchers with regards to what an explanation exactly is and which are salient properties that must be considered to make it understandable for every end-user. The SIRM introduces an xAI-white paper, which is intended to aid Radiologists, medical practitioners, and scientists in the understanding an emerging field of xAI, the black-box problem behind the success of the AI, the xAI methods to unveil the black-box into a glass-box, the role, and responsibilities of the Radiologists for appropriate use of the AI-technology. Due to the rapidly changing and evolution of AI, a definitive conclusion or solution is far away from being defined. However, one of our greatest responsibilities is to keep up with the change in a critical manner. In fact, ignoring and discrediting the advent of AI a priori will not curb its use but could result in its application without awareness. Therefore, learning and increasing our knowledge about this very important technological change will allow us to put AI at our service and at the service of the patients in a conscious way, pushing this paradigm shift as far as it will benefit us.

Brain metabolic correlates of Locus Coeruleus degeneration in Alzheimer's disease: a multimodal neuroimaging study.

Locus Coeruleus (LC) degeneration occurs early in Alzheimer's disease (AD) and this could affect several brain regions innervated by LC noradrenergic axon terminals, as these bear neuroprotective effects and modulate neurovascular coupling/neuronal activity. We used LC-sensitive Magnetic Resonance imaging (MRI) sequences enabling LC integrity quantification, and [18F]Fluorodeoxyglucose (FDG) PET, to investigate the association of LC-MRI changes with brain glucose metabolism in cognitively impaired patients (30 amnesticMCI and 13 demented ones). Fifteen cognitively intact age-matched controls (HCs) were submitted only to LC-MRI for comparison with patients. Voxel-wise regression analyses of [18F]FDG images were conducted using the LC-MRI parameters signal intensity (LCCR) and LC-belonging voxels (LCVOX). Both LCCR and LCVOX were significantly lower in patients compared to HCs, and were directly associated with [18F]FDG uptake in fronto-parietal cortical areas, mainly involving the left hemisphere (p < 0.001, kE > 100). These results suggest a possible association between LC degeneration and cortical hypometabolism in degenerative cognitive impairment with a prevalent left-hemispheric vulnerability, and that LC degeneration might be linked to large-scale functional network alteration in AD pathology.

NAVIGATOR: an Italian regional imaging biobank to promote precision medicine for oncologic patients.

NAVIGATOR is an Italian regional project boosting precision medicine in oncology with the aim of making it more predictive, preventive, and personalised by advancing translational research based on quantitative imaging and integrative omics analyses. The project's goal is to develop an open imaging biobank for the collection and preservation of a large amount of standardised imaging multimodal datasets, including computed tomography, magnetic resonance imaging, and positron emission tomography data, together with the corresponding patient-related and omics-related relevant information extracted from regional healthcare services using an adapted privacy-preserving model. The project is based on an open-source imaging biobank and an open-science oriented virtual research environment (VRE). Available integrative omics and multi-imaging data of three use cases (prostate cancer, rectal cancer, and gastric cancer) will be collected. All data confined in NAVIGATOR (i.e., standard and novel imaging biomarkers, non-imaging data, health agency data) will be used to create a digital patient model, to support the reliable prediction of the disease phenotype and risk stratification. The VRE that relies on a well-established infrastructure, called D4Science.org, will further provide a multiset infrastructure for processing the integrative omics data, extracting specific radiomic signatures, and for identification and testing of novel imaging biomarkers through big data analytics and artificial intelligence.

Interplay of tau and functional network connectivity in progressive supranuclear palsy: a [18F]PI-2620 PET/MRI study.

PURPOSE: Progressive supranuclear palsy (PSP) is primary 4-repeat tauopathy. Evidence spanning from imaging studies indicate aberrant connectivity in PSPs. Our goal was to assess functional connectivity network alterations in PSP patients and the potential link between regional tau-burden and network-level functional connectivity using the next-generation tau PET tracer [18F]PI-2620 and resting-state functional MRI (fMRI). MATERIAL AND METHODS: Twenty-four probable PSP patients (70.9 ± 6.9 years, 13 female), including 14 Richardson syndrome (RS) and 10 non-RS phenotypes, underwent [18F]PI-2620 PET/MRI imaging. Distribution volume ratios (DVRs) were estimated using non-invasive pharmacokinetic modeling. Resting-state fMRI was also acquired in these patients as well as in thirteen older non-AD MCI reference group (64 ± 9 years, 4 female). The functional network was constructed using 141 by 141 region-to-region functional connectivity metrics (RRC) and network-based statistic was carried out (connection threshold p < 0.001, cluster threshold pFDR < 0.05). RESULTS: In total, 9870 functional connections were analyzed. PSPs compared to aged non-AD MCI reference group expressed aberrant connectivity evidenced by the significant NBS network consisting of 89 ROIs and 118 connections among them (NBS mass 4226, pFDR < 0.05). Tau load in the right globus pallidus externus (GPe) and left dentate nucleus (DN) showed significant effects on functional network connectivity. The network linked with increased tau load in the right GPe was associated with hyperconnectivity of low-range intra-opercular connections (NBS mass 356, pFDR < 0.05), while the network linked with increased tau load in the left cerebellar DN was associated with cerebellar hyperconnectivity and cortico-cerebellar hypoconnectivity (NBS mass 517, pFDR < 0.05). CONCLUSIONS: PSP patients show altered functional connectivity. Network incorporating deep gray matter structures demonstrate hypoconnectivity, cerebellum hyperconnectivity, while cortico-cortical connections show variable changes. Tau load in the right GPe and left DN is associated with functional networks which strengthen low-scale intra-opercular and intra-cerebellar connections and weaken opercular-cerebellar connections. These findings support the concept of tau load-dependent functional network changes in PSP, by that providing evidence for downstream effects of neuropathology on brain functionality in this primary tauopathy.

Brain effect of bariatric surgery in people with obesity.

BACKGROUND/OBJECTIVES: The link between obesity and brain function is a fascinating but still an enigmatic topic. We evaluated the effect of Roux-en-Y gastric bypass (RYGB) on peripheral glucose metabolism, insulin sensitivity, brain glucose utilization and cognitive abilities in people with obesity. SUBJECTS/METHODS: Thirteen subjects with obesity (F/M 11/2; age 44.4 ± 9.8 years; BMI 46.1 ± 4.9 kg/m2) underwent 75-g OGTT during a [18F]FDG dynamic brain PET/CT study at baseline and 6 months after RYGB. At the same timepoints, cognitive performance was tested with Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Trail making test (TMT) and Token test (TT). Glucose, insulin, C-peptide, GLP-1, GIP, and VIP levels were measured during OGTT. Leptin and BDNF levels were measured before glucose ingestion. RESULTS: RYGB resulted in significant weight loss (from 46.1 ± 4.9 to 35.3 ± 5.0 kg/m2; p < 0.01 vs baseline). Insulin sensitivity improved (disposition index: from 1.1 ± 0.2 to 2.9 ± 1.1; p = 0.02) and cerebral glucose metabolic rate (CMRg) declined in various brain areas (all p ≤ 0.01). MMSE and MoCA score significantly improved (p = 0.001 and p = 0.002, respectively). TMT and TT scores showed a slight improvement. A positive correlation was found between CMRg change and HOMA-IR change in the caudate nucleus (ρ = 0.65, p = 0.01). Fasting leptin decreased (from 80.4 ± 13.0 to 16.1 ± 2.4 ng/dl; p = 0.001) and correlated with CMRg change in the hippocampus (ρ = 0.50; p = 0.008). CMRg change was correlated with cognitive scores changes on the TMT and TT (all p = 0.04 or less). CONCLUSIONS: Bariatric surgery improves CMRg directly related to a better cognitive testing result. This study highlights the potential pleiotropic effects of bariatric surgery. TRIAL REGISTRY NUMBER: NCT03414333.

What to Trust, PSA or [68Ga]Ga-PSMA-11: Learn from Experience.

Brain metastases from prostate cancer typically occur in the more advanced stages of the disease. Clinically, the early diagnosis of visceral disease is crucial, impacting on patient's management and prognosis. Although magnetic resonance imaging (MRI) is the modality of choice for the detection of brain metastases, it is not routinely performed in the surveillance of prostate cancer patients unless neurological manifestations appear. Prostate-specific membrane antigen (PSMA) is a glycoprotein, a membrane-bound metallopeptidase, overexpressed in more than 90% of prostate cancer cells. This molecular target is a suitable tissue biomarker for prostate cancer functional imaging. We present a case of a 73-year gentleman diagnosed with prostate adenocarcinoma and surgically treated (pT3bN1Mx, Gleason Score of 9) in February 2016. Subsequently, he underwent androgen deprivation therapy because of the occurrence of a bone metastasis. Between 2016 and January 2019 PSA levels were maintained under control. Starting from September 2019, it progressively raised up to 0.85 ng/mL with a doubling time of 3.3 months. Therefore, he performed a [68Ga]Ga-PSMA-11 PET/CT which showed a focal radiopharmaceutical uptake in the right temporal lobe corresponding to the presence of a rounded cystic lesion on brain MRI. The subsequent excisional biopsy diagnosed a prostate adenocarcinoma metastasis. PSMA expression has been reported in brain parenchyma after ischemic strokes and in some brain tumors including gliomas, meningiomas, and neurofibromas. In our case, the lack of symptoms and the relatively low PSA level raised questions about the nature of the lesion, posing the differential diagnosis between brain metastases and primary brain tumor. Finally, our case shows the capability of [68Ga]Ga-PSMA-11 PET/CT to detect metachronous distant brain metastases in a low biochemical recurrent asymptomatic prostate cancer patient, indicating that proper acquisition - from the vertex to thigh - should be always considered, regardless of the PSA level.

PET/MRI Delivers Multimodal Brain Signature in Alzheimer's Disease with De Novo PSEN1 Mutation.

BACKGROUND: Little is known so far about the brain phenotype and the spatial interplay of different Alzheimer's disease (AD) biomarkers with structural and functional brain connectivity in the early phase of autosomal-dominant AD (ADAD). Multimodal PET/MRI might be suitable to fill this gap. MATERIAL AND METHODS: We presented a 31-year-old male patient without a family history of dementia with progressive worsening of memory and motor function. Two separate sessions of 3T PET/MRI acquisitions were arranged with the ß-amyloid tracer [18F]Florbetaben and the secondgeneration tau tracer [18F]PI-2620. Simultaneously acquired MRI consisted of high-resolution 3D T1, diffusion-tensor imaging (DTI), and resting-state fMRI. PET/MRI data were compared with ten age-matched healthy controls. RESULTS: Widespread ß-amyloid depositions were found in cortical regions, and striatum (Thal stage III) along with tau pathology restricted to the mesial-temporal structures (Braak stage III/IV). Volumetric/shape analysis of subcortical structures revealed atrophy of the hippocampal-amygdala complex. In addition, cortical thinning was detected in the right middle temporal pole. Alterations of multiple DTI indices were noted in the major white matter fiber bundles, together with disruption of default mode and sensory-motor network functional connectivity. Molecular genetic analysis by next-generation sequencing revealed a heterozygote missense pathogenic variant of the PSEN1 (Met233Val). CONCLUSION: Multimodal PET/MR imaging is able to deliver, in a one-stop-shop approach, an array of molecular, structural and functional brain information in AD due to de novo pathogenic variant, which can be studied for spatial interplay and might provide a rationale for initiating anti- amyloid/tau therapeutic approaches.

Patterns and predictors of language representation and the influence of epilepsy surgery on language reorganization in children and young adults with focal lesional epilepsy.

Mapping brain functions is crucial for neurosurgical planning in patients with drug-resistant seizures. However, presurgical language mapping using either functional or structural networks can be challenging, especially in children. In fact, most of the evidence on this topic derives from cross-sectional or retrospective studies in adults submitted to anterior temporal lobectomy. In this prospective study, we used fMRI and DTI to explore patterns of language representation, their predictors and impact on cognitive performances in 29 children and young adults (mean age at surgery: 14.6 ± 4.5 years) with focal lesional epilepsy. In 20 of them, we also assessed the influence of epilepsy surgery on language lateralization. All patients were consecutively enrolled at a single epilepsy surgery center between 2009 and 2015 and assessed with preoperative structural and functional 3T brain MRI during three language tasks: Word Generation (WG), Rhyme Generation (RG) and a comprehension task. We also acquired DTI data on arcuate fasciculus in 24 patients. We first assessed patterns of language representation (relationship of activations with the epileptogenic lesion and Laterality Index (LI)) and then hypothesized a causal model to test whether selected clinical variables would influence the patterns of language representation and the ensuing impact of the latter on cognitive performances. Twenty out of 29 patients also underwent postoperative language fMRI. We analyzed possible changes of fMRI and DTI LIs and their clinical predictors. Preoperatively, we found atypical language lateralization in four patients during WG task, in one patient during RG task and in seven patients during the comprehension task. Diffuse interictal EEG abnormalities predicted a more atypical language representation on fMRI (p = 0.012), which in turn correlated with lower attention (p = 0.036) and IQ/GDQ scores (p = 0.014). Postoperative language reorganization implied shifting towards atypical language representation. Abnormal postoperative EEG (p = 0.003) and surgical failures (p = 0.015) were associated with more atypical language lateralization, in turn correlating with worsened fluency. Neither preoperative asymmetry nor postoperative DTI LI changes in the arcuate fasciculus were observed. Focal lesional epilepsy associated with diffuse EEG abnormalities may favor atypical language lateralization and worse cognitive performances, which are potentially reversible after successful surgery.

Current radiotracers to image neurodegenerative diseases.

The term of neurodegenerative diseases covers a heterogeneous group of disorders that are distinguished by progressive degeneration of the structure and function of the nervous system such as dementias, movement disorders, motor neuron disorders, as well as some prion disorders. In recent years, a paradigm shift started for the diagnosis of neurodegenerative diseases, for which successively clinical testing is supplemented by biomarker information. In research scenarios, it was even proposed recently to substitute the current syndromic by a biological definition of Alzheimer's diseases. PET examinations with various radiotracers play an important role in providing non-invasive biomarkers and co-morbidity information in neurodegeneration. Information on co-morbidity, e.g. Aß plaques and Lewy-bodies or Aß plaques in patients with aphasia or the absence of Aß plaques in clinical AD patients are of interest to expand our knowledge about the pathogenesis of different phenotypically defined neurodegenerative diseases. Moreover, this information is also important in therapeutic trials targeting histopathological abnormalities.The aim of this review is to present an overview of the currently available radiotracers for imaging neurodegenerative diseases in research and in routine clinical settings. In this context, we also provide a short summary of the most frequent neurodegenerative diseases from a nuclear medicine point of view, their clinical and pathophysiological as well as nuclear imaging characteristics, and the resulting need for new radiotracers.

Clinical Correlates of Cerebral Amyloid Deposition in Parkinson's Disease Dementia: Evidence from a PET Study.

BACKGROUND: Dementia in Parkinson's disease (PDD) is common presumably due to combined neuropathological substrates. Amyloid-ß (Aß) plaques are well described in PDD but their contribution in synucleinopathies is still controversial. OBJECTIVE: To investigate regional [18F]Florbetapir binding and its relative contribution to cognitive dysfunction in a cohort of PDD patients and to test whether PDD patients with comorbid amyloidopathy have different clinical and neuropsychological characteristics. METHODS: 21 PDD patients, 20 with Alzheimer's disease (AD), and 9 control subjects underwent amyloid positron emission tomography (PET) imaging, neurological, and neuropsychological assessment. Radioligand binding was compared across the groups. PDD scans were interpreted qualitatively and semiquantitatively and categorized as positive or negative. Annual longitudinal Mini-Mental State Examination (MMSE) of PDD subjects was retrospectively collected in order to relate Aß burden to the course of cognitive impairment. RESULTS: [18F]Florbetapir PET imaging was positive in 11 PDD patients (52.38%) using the semi-quantitative method. There were no group differences between PDD subjects with increased cortical [18F]Florbetapir (+) and those without (-), according to demographic and clinical parameters. PDD+ performed worse on Digit Span Foward and on Rey Auditory Verbal Learning Test delayed recall than the PDD- with a significant negative correlation between global cortical retention and specific memory tests. Aß load did not correlate with MMSE ratings although PDD+ demonstrated a faster clinical progression of dementia. CONCLUSIONS: Significant Aß deposition is common in PDD patients contributing to memory impairment and driving a faster rate of cognitive decline.

Relationships Between Morphologic and Functional Patterns in the Polymicrogyric Cortex.

Polymicrogyria is a malformation of cortical folding and layering underlying different cognitive and neurological manifestations. The polymicrogyric cortex has heterogeneous morphofunctional patterns, qualitatively described at magnetic resonance imaging (MRI) by variable severity gradients and functional activations. We investigated the link between abnormal cortical folding and cortical function in order to improve surgical planning for patients with polymicrogyria and intractable epilepsy. We performed structural and functional MRI on 14 patients with perisylvian polymicrogyria and adopted surface-based methods to detect alterations of cortical thickness (CT) and local gyrification index (LGI) compared with normal cortex (30 age-matched subjects). We quantitatively assessed the grade of anatomic disruption of the polymicrogyric cortex and defined its relationship with decreased cortical function. We observed a good matching between visual analysis and morphometric measurements. CT maps revealed sparse clusters of thickening, while LGI maps disclosed circumscribed regions of maximal alteration with a uniformly decreasing centrifugal gradient. In polymicrogyric areas in which gyral and sulcal patterns were preserved, functional activation maintained the expected location, but was reduced in extent. Morphofunctional correlations, evaluated along cortico-cortical paths between maximum morphologic alterations and significant activations, identified an interindividual threshold for LGI (z-value = -1.09) beyond which functional activations were no longer identifiable.

The Precuneus - A Witness for Excessive Aß Gathering in Alzheimer's Disease Pathology.

Evidence of cortical beta-amyloid (Aß) load, assessed by Aß positron emission tomography (Aß-PET), is an established in vivo biomarker of Alzheimer's disease (AD)-related pathophysiology. Qualitative assessment of Aß-PET provides binary information; meanwhile semiquantitative approaches require a parcellation of PET image either manually or by placement of atlas-based volumes of interest. We supposed that a whole-brain approach with voxel-by-voxel standardized uptake value ratio (SUVr) parametric images may better elucidate the spatial trajectories of Aß burden along the continuum of AD. METHODS: We recruited 32 subjects with a diagnosis of probable AD dementia (ADD, n = 20) and mild cognitive impairment due to AD (MCI-AD, n = 12) according to the NIA-AA 2011 criteria. We also enrolled a control group of 6 cognitively healthy individuals (HCs) with preserved cognitive functions and negative Aß-PET scan. The PET images were spatially normalized using the AV45 PET template in the MNI brain space. Subsequently, parametric SUVr images were calculated using the whole cerebellum as a reference region. A voxel-wise analysis of covariance was used to compare (between groups) the Αß distribution pattern considering age as a nuisance covariate. RESULTS: Both ADD and MCI-AD subjects showed a widespread increase in radiotracer uptake when compared with HC participants (p < 0.001, uncorrected). After applying a multiple comparison correction (p < 0.05, corrected), a relative large cluster of increased [18F]-flor-betapir uptake was observed in the precuneus in the ADD and MCI-AD groups compared to HCs. Voxel-wise regression analysis showed a significant positive linear association between the voxel-wise SUVr values and the disease duration. CONCLUSIONS: The voxel-wise semiquantitative analysis shows that the precuneus is a region with higher vulnerability to Aß depositions when compared to other cortical regions in both MCI-AD and ADD subjects. We think that the precuneus is a promising PET-based outcome measure for clinical trials of drugs targeting brain Aß. We found a positive association between the overall Aß-PET SUVr and the disease duration suggesting that the region-specific slow saturation of Aß deposition continuously takes place as the disease progresses.

From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study.

Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS.

Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study.

BACKGROUND: Hereditary spastic paraplegias (HSP) are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system ("pure" forms). The involvement of other components of the central nervous system or of other systems is described in the "complicate" forms. The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would help both the clinical handling of these conditions and contribute to our understanding of their pathogenesis. METHODS: We applied a clinical and paraclinical protocol which included tools exploring motor and non motor functioning, neurophysiology and MRI to a composite cohort of 70 molecularly defined HSP patients aged 3 to 65, to define for each indicator its significance in detailing the presence and the severity of the pathology. RESULTS: Clinically increased deep tendon reflexes and lower limb (LL) weakness are constant findings in all patients. The "complicated" forms are characterized by peripheral motor impairment, cognitive and cerebellar involvement. The Spastic Paraplegia Rating Scale efficiently reflects the severity of functional problems and correlates with disease duration. Neurophysiology consistently documents the impairment of the central motor pathway to the LLs. Nevertheless, the upper extremities and sensory system involvement is a frequent finding. MRI diffusion tensor imaging (DTI) highlighted a significant alteration of FA and MD. Combining the sampling of the various portion of the cortico-spinal tract (CST) DTI consistently discriminated patients from controls. CONCLUSION: We propose a graded clinical and paraclinical protocol for HSP phenotype definition, indicating for each tool the discriminative and descriptive capacity. Our protocol applied to 9 different forms of HSP showed that the functional impairment often extends beyond the CST. The novel DTI approach may add significant elements in disease recognition, staging and mapping.

3D-Flair sequence at 3T in cochlear otosclerosis.

PURPOSE: To assess the capability of three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences in detecting signal alterations of the endolabyrinthine fluid in patients with otosclerosis. MATERIALS AND METHODS: 3D-FLAIR before and after (-/+) gadolinium (Gd) administration was added to the standard MR protocol and acquired in 13 patients with a clinical/audiological diagnosis of severe/profound hearing loss in otosclerosis who were candidates for cochlear implantation and in 11 control subjects using 3-T magnetic resonance imaging (MRI) equipment. The MRI signal of the fluid-filled cochlea was assessed both visually and calculating the signal intensity ratio (SIR = signal intensity cochlea/brainstem). RESULTS: We revealed no endocochlear signal abnormalities on T1-weighted -/+ Gd images for either group, while on 3D-FLAIR we found bilateral hyperintensity with enhancement after Gd administration in eight patients and bilateral hyperintensity without enhancement in one patient. No endocochlear signal abnormalities were detected in other patients or the control group. CONCLUSION: Using 3-T MRI equipment, the 3D-FLAIR -/+ Gd sequence is able to detect the blood-labyrinth barrier (BLB) breakdown responsible for alterations of the endolabyrinthine fluid in patients with cochlear otosclerosis. We believe that 3D-FLAIR +/- Gd is an excellent imaging modality to assess the intra-cochlear damage in otosclerosis patients. KEY POINTS: • Gd-enhanced T1-weighted MRI has limited application to detect intra-cochlear damage. • 3D-FLAIR is less sensitive to flux artefacts and allows multiplanar reconstruction. • Post-Gd 3D-FLAIR is advantageous as it may highlight the BLB breakdown. • Using 3D-FLAIR -/+ Gd, we were able to identify intra-cochlear signal hyperintensities. • 3D-FLAIR might be applied for monitoring disease progression and treatment response.