Localized Changes in Dentate Nucleus Shape and Magnetic Susceptibility in Friedreich Ataxia.

BACKGROUND: The dentate nuclei of the cerebellum are key sites of neuropathology in Friedreich ataxia (FRDA). Reduced dentate nucleus volume and increased mean magnetic susceptibility, a proxy of iron concentration, have been reported by magnetic resonance imaging studies in people with FRDA. Here, we investigate whether these changes are regionally heterogeneous. METHODS: Quantitative susceptibility mapping data were acquired from 49 people with FRDA and 46 healthy controls. The dentate nuclei were manually segmented and analyzed using three dimensional vertex-based shape modeling and voxel-based assessments to identify regional changes in morphometry and susceptibility, respectively. RESULTS: Individuals with FRDA, relative to healthy controls, showed significant bilateral surface contraction most strongly at the rostral and caudal boundaries of the dentate nuclei. The magnitude of this surface contraction correlated with disease duration, and to a lesser extent, ataxia severity. Significantly greater susceptibility was also evident in the FRDA cohort relative to controls, but was instead localized to bilateral dorsomedial areas, and also correlated with disease duration and ataxia severity. CONCLUSIONS: Changes in the structure of the dentate nuclei in FRDA are not spatially uniform. Atrophy is greatest in areas with high gray matter density, whereas increases in susceptibility-reflecting iron concentration, demyelination, and/or gliosis-predominate in the medial white matter. These findings converge with established histological reports and indicate that regional measures of dentate nucleus substructure are more sensitive measures of disease expression than full-structure averages. Biomarker development and therapeutic strategies that directly target the dentate nuclei, such as gene therapies, may be optimized by targeting these areas of maximal pathology. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

In vivo demonstration of globotriaosylceramide brain accumulation in Fabry Disease using MR Relaxometry.

PURPOSE: How to measure brain globotriaosylceramide (Gb3) accumulation in Fabry Disease (FD) patients in-vivo is still an open challenge. The objective of this study is to provide a quantitative, non-invasive demonstration of this phenomenon using quantitative MRI (qMRI). METHODS: In this retrospective, monocentric cross-sectional study conducted from November 2015 to July 2018, FD patients and healthy controls (HC) underwent an MRI scan with a relaxometry protocol to compute longitudinal relaxation rate (R1) maps to evaluate gray (GM) and white matter (WM) lipid accumulation. In a subgroup of 22 FD patients, clinical (FAbry STabilization indEX -FASTEX- score) and biochemical (residual α-galactosidase activity) variables were correlated with MRI data. Quantitative maps were analyzed at both global ("bulk" analysis) and regional ("voxel-wise" analysis) levels. RESULTS: Data were obtained from 42 FD patients (mean age = 42.4 ± 12.9, M/F = 16/26) and 49 HC (mean age = 42.3 ± 16.3, M/F = 28/21). Compared to HC, FD patients showed a widespread increase in R1 values encompassing both GM (pFWE = 0.02) and WM (pFWE = 0.02) structures. While no correlations were found between increased R1 values and FASTEX score, a significant negative correlation emerged between residual enzymatic activity levels and R1 values in GM (r = -0.57, p = 0.008) and WM (r = -0.49, p = 0.03). CONCLUSIONS: We demonstrated the feasibility and clinical relevance of non-invasively assessing cerebral Gb3 accumulation in FD using MRI. R1 mapping might be used as an in-vivo quantitative neuroimaging biomarker in FD patients.

Clinical correlates of R1 relaxometry and magnetic susceptibility changes in multiple sclerosis: a multi-parameter quantitative MRI study of brain iron and myelin.

OBJECTIVES: The clinical impact of brain microstructural abnormalities in multiple sclerosis (MS) remains elusive. We aimed to characterize the topography of longitudinal relaxation rate (R1) and quantitative susceptibility (χ) changes, as indices of iron and myelin, together with brain atrophy, and to clarify their contribution to cognitive and motor disability in MS. METHODS: In this cross-sectional study, voxel-based morphometry, and voxel-based quantification analyses of R1 and χ maps were conducted in gray matter (GM) and white matter (WM) of 117 MS patients and 53 healthy controls. Voxel-wise between-group differences were assessed with nonparametric permutation tests, while correlations between MRI metrics and clinical variables (global disability, cognitive and motor performance) were assessed both globally and voxel-wise within clusters emerging from the between-group comparisons. RESULTS: MS patients showed widespread R1 decrease associated with more limited modifications of χ, with atrophy mainly involving deep GM, posterior and infratentorial regions (p < 0.02). While R1 and χ showed a parallel reduction in several WM tracts (p < 0.001), reduced GM R1 values (p < 0.001) were associated with decreased thalamic χ (p < 0.001) and small clusters of increased χ in the caudate nucleus and prefrontal cortex (p < 0.02). In addition to the atrophy, χ values in the cingulum and corona radiata correlated with global disability and motor performance, while focal demyelination correlated with cognitive performance (p < 0.04). CONCLUSIONS: We confirmed the presence of widespread R1 changes, involving both GM and WM, and atrophy in MS, with less extensive modifications of tissue χ. While atrophy and χ changes are related to global and motor disability, R1 changes are meaningful correlates of cognition. KEY POINTS: • Compared to healthy controls, multiple sclerosis patients showed R1 and χ changes suggestive of iron increase within the basal ganglia and reduced iron and myelin content within (subnuclei of) the thalamus. • Thalamic volume and χ changes significantly predicted clinical disability, as well as pulvinar R1 and χ changes, independently from atrophy. • Atrophy-independent R1 and χ changes, suggestive of thalamic iron and myelin depletion, may represent a sensitive marker of subclinical inflammation.

The central vein sign helps in differentiating multiple sclerosis from its mimickers: lessons from Fabry disease.

OBJECTIVES: Although the use of specific MRI criteria has significantly increased the diagnostic accuracy of multiple sclerosis (MS), reaching a correct neuroradiological diagnosis remains a challenging task, and therefore the search for new imaging biomarkers is crucial. This study aims to evaluate the incidence of one of the emerging neuroradiological signs highly suggestive of MS, the central vein sign (CVS), using data from Fabry disease (FD) patients as an index of microvascular disorder that could mimic MS. METHODS: In this retrospective study, after the application of inclusion and exclusion criteria, MRI scans of 36 FD patients and 73 relapsing-remitting (RR) MS patients were evaluated. Among the RRMS participants, 32 subjects with a disease duration inferior to 5 years (early MS) were also analyzed. For all subjects, a Fazekas score (FS) was recorded, excluding patients with FS = 0. Different neuroradiological signs, including CVS, were evaluated on FLAIR T2-weighted and spoiled gradient recalled echo sequences. RESULTS: Among all the recorded neuroradiological signs, the most striking difference was found for the CVS, with a detectable prevalence of 78.1% (57/73) in RRMS and of 71.4% (25/32) in early MS patients, while this sign was absent in FD (0/36). CONCLUSIONS: Our results confirm the high incidence of CVS in MS, also in the early phases of the disease, while it seems to be absent in conditions with a different etiology. These results corroborate the possible role of CVS as a useful neuroradiological sign highly suggestive of MS. KEY POINTS: • The search for new imaging biomarkers is crucial to achieve a correct neuroradiological diagnosis of MS. • The CVS shows an incidence superior to 70% in MS patients, even in the early phases of the disease, while it appears to be absent in FD. • These findings further corroborate the possible future central role of CVS in distinguishing between MS and its mimickers.

Bringing radiomics into a multi-omics framework for a comprehensive genotype-phenotype characterization of oncological diseases.

Genomic and radiomic data integration, namely radiogenomics, can provide meaningful knowledge in cancer diagnosis, prognosis and treatment. Despite several data structures based on multi-layer architecture proposed to combine multi-omic biological information, none of these has been designed and assessed to include radiomic data as well. To meet this need, we propose to use the MultiAssayExperiment (MAE), an R package that provides data structures and methods for manipulating and integrating multi-assay experiments, as a suitable tool to manage radiogenomic experiment data. To this aim, we first examine the role of radiogenomics in cancer phenotype definition, then the current state of radiogenomics data integration in public repository and, finally, challenges and limitations of including radiomics in MAE, designing an extended framework and showing its application on a case study from the TCGA-TCIA archives. Radiomic and genomic data from 91 patients have been successfully integrated in a single MAE object, demonstrating the suitability of the MAE data structure as container of radiogenomic data.

A multi-parametric PET/MRI study of breast cancer: Evaluation of DCE-MRI pharmacokinetic models and correlation with diffusion and functional parameters.

46 patients with histologically confirmed breast cancer were enrolled and imaged with a 3T hybrid PET/MRI system, at staging. Diffusion, functional and perfusion parameters (measured by Tofts and shutter speed models) were compared. Results showed a good correlation between pharmacokinetic parameters and the SUV.

Pilot study of rapid MR pancreas screening for patients with BRCA mutation.

PURPOSE: To develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in breast cancer susceptibility gene (BRCA)-positive individuals. METHODS: An IRB-approved prospective study was conducted. The rapid screening pancreatic MR protocol was designed to be less than 10 min to be performed after a standard breast MRI protocol. Protocol consisted of coronal NT T2 SSFSE, axial NT T2 SSFSE and axial NT rFOV FOCUS DWI, and axial T1. Images were acquired with the patient in the same prone position of breast MRI using the built-in body coil. Image quality was qualitatively assessed by two radiologists with 12 and 13 years of MRI experience, respectively. The imaging protocol was modified until an endpoint of five consecutive patients with high-quality diagnostic images were achieved. Signal-to-noise ratio and contrast-to-noise ratio were assessed. RESULTS: The rapid pancreas MR protocol was successfully completed in all patients. Diagnostic image quality was achieved for all patients. Excellent image quality was achieved for low b values; however, image quality at higher b values was more variable. In one patient, a pancreatic neuroendocrine tumor was found and the patient was treated surgically. In four patients, small pancreatic cystic lesions were detected. In one subject, a hepatic mass was identified and confirmed as adenoma by liver MRI. CONCLUSION: Rapid MR protocol for pancreatic cancer screening is feasible and has the potential to play a role in screening BRCA patients undergoing breast MRI. KEY POINT: • Develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in BRCA mutation positive individuals.

MRI features suggestive of gadolinium retention do not correlate with Expanded Disability Status Scale worsening in Multiple Sclerosis.

PURPOSE: Different studies showed correlations between gadolinium-based contrast agent (GBCA) administrations and dentate nucleus (DN) T1-weighted hyperintensity. The clinical impact of gadolinium retention, however, is still largely unknown. The aim of this study was to investigate relations between MRI and clinical disability in relapsing-remitting multiple sclerosis (RR-MS) patients. METHODS: In this retrospective study, clinical data were obtained from 74 RR-MS patients at baseline and after a mean follow-up time of 3.6 years, including the expanded disability status scale (EDSS) score and its change (ΔEDSS). Patients were considered showing clinical worsening if they score a ΔEDSS ≥ 1 (for baseline EDSS ≤ 5.5) or ΔEDSS ≥ 0.5 (for baseline EDSS > 5.5). From the MRI data, the presence of bilateral DN hyperintensity was recorded along with the calculation of longitudinal relaxation rate (R1) maps. RESULTS: Patients with DN hyperintensity showed similar ΔEDSS change compared to those without visible changes on T1-weighted images (p = 0.32). Similarly, no DN-R1 difference was found comparing stable patients with those showing a significant clinical worsening (p = 0.54). Finally, no significant effect of DN-R1 values explained the variance in ΔEDSS (p = 0.76), thus suggesting their independence from the clinical outcome. CONCLUSIONS: MS patients with DN hyperintensity show similar EDSS changes compared to subjects without DN high-signal intensity. Furthermore, mean DN-R1 values of patients with significant clinical worsening were comparable to those of stable subjects and were unrelated to clinical disability. Taken together, these findings suggest that gadolinium retention in the brain of MS patients does not affect their clinical worsening, expressed by the EDSS change.

Treatment-related Focal Nodular Hyperplasia Mimicking Liver Metastases.

A 7-year-old patient with a stage 4 neuroblastoma underwent chemotherapy, surgery, myeloablative therapy, external beam radiotherapy, and Isoretinoin treatment. A posttreatment magnetic resonance examination performed administering gadoteric acid as contrast agent showed 2 new hypervascular hepatic lesions, suspicious for metastases. A second magnetic resonance imaging performed using a liver-specific contrast medium (gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid) demonstrated that these lesions were consistent with treatment-related focal nodular hyperplasia.

Comparison of Navigator Triggering Reduced Field of View and Large Field of View Diffusion-Weighted Imaging of the Pancreas.

RATIONALE AND OBJECTIVES: The purpose of this study is to compare image quality, presence and grade of artifacts, signal-to-noise ratio, and apparent diffusion coefficient (ADC) values in pancreatic tissue between high-resolution navigator-triggered (NT) restricted field of view (rFOV) FOCUS single-shot (SS) echo-planar imaging (EPI) diffusion-weighted imaging (DWI) and NT large FOV SS-EPI DWI. MATERIALS AND METHODS: Magnetic resonance imaging examinations were performed with GE 3-T systems using a 32-channel body array coil. Seventeen consecutive patients were imaged. A 5-point scale semiquantitative grading system was used to evaluate image quality and general artifacts. Signal-to-noise ratio and ADC were measured in the head, body, and tail of the pancreas. Statistical analysis was performed using Student t test and Wilcoxon signed rank test, with differences considered significant for P value less than 0.05. RESULTS: More artifacts were present on large FOV compared with rFOV FOCUS SS-EPI DW images (P < 0.01). Restricted field of view image quality was subjectively better (P < 0.01). No difference in the signal-to-noise ratio was demonstrated between the 2 image datasets. Apparent diffusion coefficient values were significantly lower (P < 0.01) when calculated from rFOV images than large FOV images. CONCLUSIONS: Our results demonstrate better image quality and reduced artifacts in rFOV images compared with large FOV DWI. Measurements from ADC maps derived from rFOV DWI show significantly lower ADC values when compared with ADC maps derived from large FOV DWI.

Relationship between functional imaging and immunohistochemical markers and prediction of breast cancer subtype: a PET/MRI study.

PURPOSE: The aim of this study was to determine if functional parameters extracted from the hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) correlate with the immunohistochemical markers of breast cancer (BC) lesions, to assess their ability to predict BC subtype. METHODS: This prospective study was approved by the institution's Ethics Committee, and all patients provided written informed consent. A total of 50 BC patients at diagnosis underwent PET/MRI before pharmacological and surgical treatment. For each primary lesion, the following data were extracted: morphological data including tumour-node-metastasis stage and lesion size; apparent diffusion coefficient (ADC); perfusion data including forward volume transfer constant (Ktrans), reverse efflux volume transfer constant (Kep) and extravascular extracellular space volume (Ve); and metabolic data including standardized uptake value (SUV), lean body mass (SUL), metabolic tumour volume and total lesion glycolysis. Immunohistochemical reports were used to determine receptor status (oestrogen, progesterone, and human epidermal growth factor receptor 2), cellular differentiation status (grade), and proliferation index (Ki67) of the tumour lesions. Correlation studies (Mann-Whitney U test and Spearman's test), receiver operating characteristic (ROC) curve analysis, and multivariate analysis were performed. RESULTS: Association studies were performed to assess the correlations between imaging and histological prognostic markers of BC. Imaging biomarkers, which significantly correlated with biological markers, were selected to perform ROC curve analysis to determine their ability to discriminate among BC subtypes. SUVmax, SUVmean and SUL were able to discriminate between luminal A and luminal B subtypes (AUCSUVmean = 0.799; AUCSUVmax = 0.833; AUCSUL = 0.813) and between luminal A and nonluminal subtypes (AUCSUVmean = 0.926; AUCSUVmax = 0.917; AUCSUL = 0.945), and the lowest SUV and SUL values were associated with the luminal A subtype. Kepmax was able to discriminate between luminal A and luminal B subtypes (AUC = 0.779), and its highest values were associated with the luminal B subtype. Ktransmax (AUC = 0.881) was able to discriminate between luminal A and nonluminal subtypes, and the highest perfusion values were associated with the nonluminal subtype. In addition, ADC (AUC = 0.877) was able to discriminate between luminal B and nonluminal subtypes, and the lowest ADCmean values were associated with the luminal B subtype. Multivariate analysis was performed to develop a prognostic model, and the best predictive model included Ktransmax and SUVmax parameters. CONCLUSION: Using multivariate analysis of both PET and MRI parameters, a prognostic model including Ktransmax and SUVmax was able to predict the tumour subtype in 38 of 49 patients (77.6%, p < 0.001), with higher accuracy for the luminal B subtype (86.2%).

Radiogenomic Analysis of Oncological Data: A Technical Survey.

In the last few years, biomedical research has been boosted by the technological development of analytical instrumentation generating a large volume of data. Such information has increased in complexity from basic (i.e., blood samples) to extensive sets encompassing many aspects of a subject phenotype, and now rapidly extending into genetic and, more recently, radiomic information. Radiogenomics integrates both aspects, investigating the relationship between imaging features and gene expression. From a methodological point of view, radiogenomics takes advantage of non-conventional data analysis techniques that reveal meaningful information for decision-support in cancer diagnosis and treatment. This survey is aimed to review the state-of-the-art techniques employed in radiomics and genomics with special focus on analysis methods based on molecular and multimodal probes. The impact of single and combined techniques will be discussed in light of their suitability in correlation and predictive studies of specific oncologic diseases.

Dual energy computed tomography quantification of carotid plaques calcification: comparison between monochromatic and polychromatic energies with pathology correlation.

PURPOSE: We compared carotid plaque calcification detection sensitivity and apparent cross-sectional area on CT as a function of CT beam energy using conventional CT techniques and virtual mono-energetic CT images generated from dual-energy acquisitions. METHODS & MATERIALS: Five ex-vivo carotid endarterectomy (CEA) specimens were imaged with dual-energy computed tomography. Virtual monochromatic spectrum (VMS) CT images were reconstructed at energies between 40-140 keV. The same specimens were imaged using conventional polyenergetic spectrum (PS) CT with peak beam energies 80, 100, 120, and 140 kVp. The histological calcium areas on each corresponding CEA specimen were traced manually on digitized images of Toluidine-Blue/Basic-Fuchsin stained plastic sections. RESULTS: 40 keV VMS CT images provided high detection sensitivity (97 %) similar to conventional PS CT images (~96 %). The calcification size measured on CT decreased systematically with increasing CT beam energy; the rate of change was larger for the VMS images than for PS images. CONCLUSION: From a single dual-energy CT, multiple VMS-CT images can be generated, yielding equivalent detection sensitivity and size correlations as conventional PS-CT in CEA calcification imaging. VMS-CT at 80-100 keV provided the most accurate estimates of calcification size, as compared to histology, but detection sensitivity was reduced for smaller calcifications on these images. KEY POINTS: • Calcifications depicted at 80-100 keV were most similar to the histology standard. • Conventional polychromatic images demonstrated excellent correlation with plaque size at pathology. • Conventional polychromatic images systematically overestimate plaque size. • Plaque calcifications can be missed on high energy monochromatic images.

Uncommon pancreatic tumors and pseudotumors.

A heterogeneous group of uncommon neoplastic and non-neoplastic pancreatic pathologies exists that can mimic pancreatic adenocarcinoma. These "imitators" are unique and may demonstrate characteristic clinical and imaging features. Imaging characteristics of some of these diverse lesions are not well described in the literature, and erroneous diagnoses of these entities as pancreatic carcinoma may be responsible for unnecessary surgeries. Knowledge of these selected pancreatic pathologies is essential to facilitate optimal patient management.

Nuclear medicine and the emergency department patient: an illustrative case-based approach.

Radiologists are familiar with the use of radiographs, computed tomography, magnetic resonance imaging and ultrasound in the acute clinical setting. However, there are some specific clinical scenarios which may be found in nuclear medicine imaging problem-solving tools. These clinical scenarios and imaging techniques are less frequent, and the referring clinician from the emergency department may not consider these alternatives. It is important for the radiologist to be aware of these techniques to be able to guide the clinician to use those tools, which may result in optimal patient care. In this article, we will discuss those nuclear medicine studies which have application in the setting of an emergency radiology practice.

Modeling frameworks for radiation induced lymphopenia: A critical review.

Radiation-induced lymphopenia (RIL) is a frequent, and often considered unavoidable, side effect of radiation therapy (RT), whether or not chemotherapy is included. However, in the last few years several studies have demonstrated the detrimental effect of RIL on therapeutic outcomes, with conflicting findings concerning possible inferior patient survival. In addition, since immunotherapeutic treatment has become an integral part of cancer therapy, preserving the immune system is recognized as crucial. Given this background, various research groups have reported on different frameworks for modelling RIL, frequently based on different definitions of RIL itself, and discordant results have been reported. Our aim is to critically review the current literature on RIL modelling and summarize the different approaches recently proposed to improve the prediction of RIL after RT and aimed at immunity-sparing RT. A detailed description of these approaches will be outlined and illustrated through their applications as found in the literature from the last five years. Such a critical analysis represents the necessary starting step to develop an effective strategy that ultimately could harmonize the diverse modelling methods.

Incidence of alopecia in brain tumour patients treated with pencil scanning proton therapy and validation of existing NTCP models.

BACKGROUND AND PURPOSE: Radiation-induced alopecia (RIA) is one of the most frequent and upsetting cosmetic side effects after radiotherapy (RT) for brain cancer. We report the incidence of RIA in a cohort of brain tumours patients treated with Proton Therapy (PT) and externally validate published NTCP models of grade 2 (G2) RIA for their implementation in clinical practice. METHODS: Data for patients treated for brain tumours with scanning beam PT between 2018 and 2022 were extracted. Acute, late and permanent RIA events were evaluated according to CTCAE 5.0. Lyman-Kutcher-Burman (LKB) and multivariable logistic regression (MLR) published models were computed from the relative dose-surface histogram of the scalp. External validity of models was assessed in terms of discrimination and calibration. RESULTS: In the 264 patients analysed, rates of any grade acute (≤90 days after PT completion), late (>90 days) and permanent RIA (persisting for> 12 months) were 61.8 %, 24.7 % and 14.4 %, respectively. In our independent cohort, LKB- and MLR-NTCP showed a good discrimination for G2 RIA (0.71≤ROC-AUC≤0.83) while model calibration was unsatisfactory possibly due to a different outcome evaluation between training and validation cohorts, as well as differences in clinical and treatment related variables between the two groups. CONCLUSIONS: Despite the reasonable sensitivity and specificity of the NTCP models for RIA in the validation cohort, our study emphasizes the significance of differences between the cohorts utilized for model development and validation. Specifically, variations in the reporting of clinical outcomes inevitably jeopardize the validation of NTCP models. A standardize and objective RIA scoring system is essential.

Gradient of microstructural damage along the dentato-thalamo-cortical tract in Friedreich ataxia.

OBJECTIVE: The dentato-thalamo-cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach. METHODS: MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross-sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison. RESULTS: Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted. INTERPRETATION: Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex.