Ultrathin Gd-Oxide Nanosheet as Ultrasensitive Companion Diagnostic Tool for MR Imaging and Therapy of Submillimeter Microhepatocellular Carcinoma.

Early stage hepatocellular carcinoma (HCC) presents a formidable challenge in clinical settings due to its asymptomatic progression and the limitations of current imaging techniques in detecting micro-HCC lesions. Addressing this critical issue, we introduce a novel ultrathin gadolinium-oxide (Gd-oxide) nanosheet-based platform with heightened sensitivity for high-field MRI and as a therapeutic agent for HCC. Synthesized via a digestive ripening process, these Gd-oxide nanosheets exhibit an exceptional acid-responsive profile. The integration of the ultrathin Gd-oxide with an acid-responsive polymer creates an ultrasensitive high-field MRI probe, enabling the visualization of submillimeter-sized tumors with superior sensitivity. Our research underscores the ultrasensitive probe's efficacy in the treatment of orthotopic HCC. Notably, the ultrasensitive probe functions dually as a companion diagnostic tool, facilitating simultaneous imaging and therapy with real-time treatment monitoring capabilities. In conclusion, this study showcases an innovative companion diagnostic tool that holds promise for the early detection and effective treatment of micro-HCC.

Knowledge-driven deep learning for fast MR imaging: Undersampled MR image reconstruction from supervised to un-supervised learning.

Deep learning (DL) has emerged as a leading approach in accelerating MRI. It employs deep neural networks to extract knowledge from available datasets and then applies the trained networks to reconstruct accurate images from limited measurements. Unlike natural image restoration problems, MRI involves physics-based imaging processes, unique data properties, and diverse imaging tasks. This domain knowledge needs to be integrated with data-driven approaches. Our review will introduce the significant challenges faced by such knowledge-driven DL approaches in the context of fast MRI along with several notable solutions, which include learning neural networks and addressing different imaging application scenarios. The traits and trends of these techniques have also been given which have shifted from supervised learning to semi-supervised learning, and finally, to unsupervised learning methods. In addition, MR vendors' choices of DL reconstruction have been provided along with some discussions on open questions and future directions, which are critical for the reliable imaging systems.

Physics-guided self-supervised learning for retrospective T1 and T2 mapping from conventional weighted brain MRI: Technical developments and initial validation in glioblastoma.

PURPOSE: To develop a self-supervised learning method to retrospectively estimate T1 and T2 values from clinical weighted MRI. METHODS: A self-supervised learning approach was constructed to estimate T1, T2, and proton density maps from conventional T1- and T2-weighted images. MR physics models were employed to regenerate the weighted images from the network outputs, and the network was optimized based on loss calculated between the synthesized and input weighted images, alongside additional constraints based on prior information. The method was evaluated on healthy volunteer data, with conventional mapping as references. The reproducibility was examined on two 3.0T scanners. Performance in tumor characterization was inspected by applying the method to a public glioblastoma dataset. RESULTS: For T1 and T2 estimation from three weighted images (T1 MPRAGE, T1 gradient echo sequences, and T2 turbo spin echo), the deep learning method achieved global voxel-wise error ≤9% in brain parenchyma and regional error ≤12.2% in six types of brain tissues. The regional measurements obtained from two scanners showed mean differences ≤2.4% and correlation coefficients >0.98, demonstrating excellent reproducibility. In the 50 glioblastoma patients, the retrospective quantification results were in line with literature reports from prospective methods, and the T2 values were found to be higher in tumor regions, with sensitivity of 0.90 and specificity of 0.92 in a voxel-wise classification task between normal and abnormal regions. CONCLUSION: The self-supervised learning method is promising for retrospective T1 and T2 quantification from clinical MR images, with the potential to improve the availability of quantitative MRI and facilitate brain tumor characterization.

Assessment for Carotid Atherosclerotic Plaque Using Vessel Wall Magnetic Resonance Imaging: A Multireader ROC Study to Determine Optimal Sequence for Detecting Vessel Wall Calcification.

INTRODUCTION: We aimed to compare conventional vessel wall MR imaging techniques and quantitative susceptibility mapping (QSM) to determine the optimal sequence for detecting carotid artery calcification. METHODS: Twenty-two patients who underwent carotid vessel wall MR imaging and neck CT were enrolled. Four slices of 6-mm sections from the bilateral internal carotid bifurcation were subdivided into 4 segments according to clock position (0-3, 3-6, 6-9, and 9-12) and assessed for calcification. Two blinded radiologists independently reviewed a total of 704 segments and scored the likelihood of calcification using a 5-point scale on spin-echo imaging, FLASH, and QSM. The observer performance for detecting calcification was evaluated by a multireader, multiple-case receiver operating characteristic study. Weighted κ statistics were calculated to assess interobserver agreement. RESULTS: QSM had a mean area under the receiver operating characteristic curve of 0.85, which was significantly higher than that of any other sequence (p < 0.01) and showed substantial interreader agreement (κ = 0.68). A segment with a score of 3-5 was defined as positive, and a segment with a score of 1-2 was defined as negative; the sensitivity and specificity of QSM were 0.75 and 0.87, respectively. CONCLUSION: QSM was the most reliable MR sequence for the detection of plaque calcification.

Fast high-resolution electric properties tomography using three-dimensional quantitative transient-state imaging-based water fraction estimation.

In this study, we aimed to develop a fast and robust high-resolution technique for clinically feasible electrical properties tomography based on water content maps (wEPT) using Quantitative Transient-state Imaging (QTI), a multiparametric transient state-based method that is similar to MR fingerprinting. Compared with the original wEPT implementation based on standard spin-echo acquisition, QTI provides robust electrical properties quantification towards B1 + inhomogeneities and full quantitative relaxometry data. To validate the proposed approach, 3D QTI data of 12 healthy volunteers were acquired on a 1.5 T scanner. QTI-provided T1 maps were used to compute water content maps of the tissues using an empirical relationship based on literature ex-vivo measurements. Assuming that electrical properties are modulated mainly by tissue water content, the water content maps were used to derive electrical conductivity and relative permittivity maps. The proposed technique was compared with a conventional phase-only Helmholtz EPT (HH-EPT) acquisition both within whole white matter, gray matter, and cerebrospinal fluid masks, and within different white and gray matter subregions. In addition, QTI-based wEPT was retrospectively applied to four multiple sclerosis adolescent and adult patients, compared with conventional contrast-weighted imaging in terms of lesion delineation, and quantitatively assessed by measuring the variation of electrical properties in lesions. Results obtained with the proposed approach agreed well with theoretical predictions and previous in vivo findings in both white and gray matter. The reconstructed maps showed greater anatomical detail and lower variability compared with standard phase-only HH-EPT. The technique can potentially improve delineation of pathology when compared with conventional contrast-weighted imaging and was able to detect significant variations in lesions with respect to normal-appearing tissues. In conclusion, QTI can reliably measure conductivity and relative permittivity of brain tissues within a short scan time, opening the way to the study of electric properties in clinical settings.

High b-Value and Ultra-High b-Value Diffusion Weighted MRI in Stroke.

PURPOSE: To explore the application value of high-b-value and ultra-high b-value DWI in noninvasive evaluation of ischemic infarctions. STUDY TYPE: Prospective. SUBJECTS: Sixty-four patients with clinically diagnosed ischemic lesions based on symptoms and DWI. FIELD STRENGTH/SEQUENCE: 3.0 T/T2-weighted fast spin-echo, fluid-attenuated inversion recovery, pre-contrast T1-weighted magnetization prepared rapid gradient echo sequence, multi-b-value trace DWI and q-space sampling sequences. ASSESSMENT: Lesions were segmented on standard b-value DWI (SB-DWI, 1000 s/mm2), high b-value DWI (HB-DWI, 4000 s/mm2) and ultra-high b-value DWI (UB-DWI, 10,000 s/mm2), and cumulative segmented areas were the final abnormality volumes. Normal white matter (WM) areas were obtained after binarization of segmented brain. In 47 patients, fractional anisotropy (FA) and apparent diffusion coefficients (ADCs) at b values of 1000, 4000, and 10,000 s/mm2 were extracted from symmetrical WM masks and lesion masks of contralateral WM (CWM) and lesion-side WM (LWM). STATISTICAL TESTS: Wilcoxon matched-pairs signed-rank test and Pearson correlation analysis. Two-tailed P-values <0.05 were considered statistically significant. RESULTS: Various signals of HB-/UB-DWI (hypo-, iso- or hyper-intensity) were observed in strokes compared with SB-DWI, and some areas with iso-intensity of SB-DWI manifested with hyper-intensity on HB-/UB-DWI. Abnormality volumes from SB-DWI were significantly smaller than those from HB-DWI and UB-DWI (10.32 ± 16.45 cm3, vs. 12.25 ± 19.71 cm3 and 11.83 ± 19.41 cm3), while no significant difference exist in volume between HB-DWI and UB-DWI (P = 0.32). In CWM, FA significantly correlated with ADC4000 and ADC10,000 (maximum r = -0.51 and -0.64), but did not significantly correlate with ADC1000 (maximum r = -0.20, P = 0.17). ADC1000 or ADC4000 of LWM not significant correlated with FA of CWM (maximum r = -0.28, P = 0.06), while ADC10,000 of LWM significantly correlated with FA of CWM (maximum r = -0.46). DATA CONCLUSION: HB- and UB-DWI have potential to be supplementary tools for the noninvasive evaluation of stroke lesions in clinics. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Clinical and neuroimaging precursors in cerebral amyloid angiopathy: impact of the Boston criteria version 2.0.

BACKGROUND AND PURPOSE: Although the Boston criteria version 2.0 facilitates the sensitivity of cerebral amyloid angiopathy (CAA) diagnosis, there are only limited data about precursor symptoms. This study aimed to determine the impact of neurological and imaging features in relation to the time of CAA diagnosis. METHODS: Patients diagnosed with probable CAA according to the Boston criteria version 1.5, treated between 2010 and 2020 in our neurocentre, were identified through a keyword search in our medical database. Neuroimaging was assessed using Boston criteria versions 1.5 and 2.0. Medical records with primary focus on the clinical course and the occurrence of transient focal neurological episodes were prospectively evaluated. RESULTS: Thirty-eight out of 81 patients (46.9%) exhibited transient focal neurological episodes, most often sensory (13.2%) or aphasic disorders (13.2%), or permanent deficits at a mean time interval of 31.1 months (SD ±26.3; range 1-108 months) before diagnosis of probable CAA (Boston criteria version 1.5). If using Boston criteria version 2.0, all patients receiving magnetic resonance imaging (MRI) met the criteria for probable CAA, and diagnosis could have been made on average 44 months earlier. Four patients were younger than 50 years, three of them with supporting pathology. Cognitive deficits were most common (34.6%) at the time of diagnosis. CONCLUSIONS: Non-haemorrhagic MRI markers enhance the sensitivity of diagnosing probable CAA; however, further prospective studies are proposed to establish a minimum age for inclusion. As the neurological overture of CAA may occur several years before clinical diagnosis, early clarification by MRI including haemosensitive sequences are suggested.

Facile synthesis of Gd/Ru-doped fluorescent carbon dots for fluorescent/MR bimodal imaging and tumor therapy.

Functional metal doping endows fluorescent carbon dots with richer physical and chemical properties, greatly expanding their potential in the biomedical field. Nonetheless, fabricating carbon dots with integrated functionality for diagnostic and therapeutic modalities remains challenging. Herein, we develop a simple strategy to prepare Gd/Ru bimetallic doped fluorescent carbon dots (Gd/Ru-CDs) via a one-step microwave-assisted method with Ru(dcbpy)3Cl2, citric acid, polyethyleneimine, and GdCl3 as precursors. Multiple techniques were employed to characterize the morphology and properties of the obtained carbon dots. The Gd/Ru-CDs are high mono-dispersity, uniform spherical nanoparticles with an average diameter of 4.2 nm. Moreover, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR) confirmed the composition and surface properties of the carbon dots. In particular, the successful doping of Gd/Ru enables the carbon dots not only show considerable magnetic resonance imaging (MRI) performance but also obtain better fluorescence (FL) properties, especially in the red emission area. More impressively, it has low cytotoxicity, excellent biocompatibility, and efficient reactive oxygen species (ROS) generation ability, making it an effective imaging-guided tumor treatment reagent. In vivo experiments have revealed that Gd/Ru-CDs can achieve light-induced tumor suppression and non-invasive fluorescence/magnetic resonance bimodal imaging reagents to monitor the treatment process of mouse tumor models. Thus, this simple and efficient carbon dot manufacturing strategy by doping functional metals has expanded avenues for the development and application of multifunctional all-in-one theranostics.

A comprehensive MRI investigation to identify potential biomarkers of Osgood Schlatter disease in adolescents: A cross sectional study comparing Osgood Schlatter disease with controls.

BACKGROUND: Osgood-Schlatter disease (OSD) is the most common knee pain complaint among adolescents playing sports. Despite this, there remains controversy over the pathophysiology and whether specific anatomical characteristics are associated with OSD. PURPOSE: This study aimed to systematically and comprehensively characterize adolescents with OSD using magnetic resonance imaging (MRI) compared to pain-free controls, including both tissue abnormalities that may be associated with OSD, as well as anatomical characteristics. A secondary objective was to identify potential imaging biomarkers associated with pain. STUDY DESIGN: Cross-sectional study. METHODS: Adolescents with OSD and controls were recruited from 2020 to 2022. Following a clinical exam, demographics, pain, sports participation, and Tanner stage were collected. Knee MRI was conducted on the participants' most symptomatic knee (OSD) or the dominant leg (controls). RESULTS: Sixty-seven adolescents (46 with OSD and 30 controls) were included. 80% of participants with OSD had at least one tissue alteration compared to 54% of controls. Compared to controls, OSD had 36.3 (95%CI 4.5 to 289.7) higher odds of bony oedema at the tibial tuberosity, and 32.7 (95%CI 4.1 to 260.6) and 5.3 (95%CI 0.6 to 46.2) higher odds of bony oedema at the  tibial epiphysis and metaphysis respectively. Participants with OSD also had higher odds of fluid/oedema at the patellar tendon (12.3 95%CI 3.3 to 46.6), and superficial infrapatellar bursitis (7.2).  Participants with OSD had a more proximal tendon attachment (mean tibial attachment portion difference, -0.05, 95% CI: -0.1 to 0.0, p = 0.02), tendon thickness (proximal mean difference, -0.09, 95% CI: -0.4 to 0.2, p = 0.04; distal mean difference, -0.6, 95% CI: -0.9 to -0.2, p = 0.01). Those with bony/tendon oedema had 1.8 points (95% CI: 0.3 to 3.2) higher pain on palpation than those without (t = -2.5, df = 26.6, p = 0.019), but there was no difference between these groups in a functional single leg pain provocation. CONCLUSION: Adolescents with OSD present with tissue and structural abnormalities on MRI that differed from age-matched controls. The majority had findings in the patellar tendon and bone, which often co-occurred. However, a small proportion of OSD also presents without alterations. It appears these findings may be associated with clinical OSD-related pain on palpation of the tibial tuberosity. CLINICAL RELEVANCE: Our highlight the pathophysiology on imaging, which has implications for understanding the mechanism and treatment of OSD.

Successful treatment of respiratory failure in Hirayama disease.

Hirayama disease is a self-limiting cervical motor neuron disease, usually affecting the spinal cord at level C7-T1. We share an unusual case of Hirayama disease in a young man affecting roots C4-C6. He presented in coma due to diaphragm weakness and hypercapnic respiratory failure. Diagnosis was achieved via clinical presentation, neurophysiological examination, ultrasonography of the diaphragm and dynamic MR-imaging. Conservative treatment with a cervical collar resulted in remarkable improvement in respiratory and motor function.

Histology and chronological magnetic resonance images of congenital spinal deformity: An experimental study in mice model.

BACKGROUND: The natural history of the congenital spinal deformity and its clinical magnitude vary widely in human species. However, we previously reported that the spinal deformities of congenital scoliosis mice did not progress throughout our observational period according to soft X-ray and MRI data. In this study, congenital vertebral and intervertebral malformations in mice were assessed via magnetic resonance (MR) and histological images. METHODS: Congenital spinal anomalies were chronologically assessed via soft X-ray and 7 T MR imaging. MR images were compared to the histological images to validate the findings around the malformations. RESULTS: Soft X-ray images showed the gross alignment of the spine and the contour of the malformed vertebrae, with the growth plate and cortical bone visible as higher density lines, but could not be used to distinguish the existence of intervertebral structures. In contrast, MR images could be used to distinguish each structure, including the cortical bone, growth plate, cartilaginous end plate, and nucleus pulposus, by combining the signal changes on T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI). The intervertebral structure adjacent to the malformed vertebrae also exhibited various abnormalities, such as growth plate and cartilaginous end plate irregularities, nucleus pulposus defects, and bone marrow formation. In the chronological observation, the thickness and shape of the malformed structures on T1WI did not change. CONCLUSIONS: Spinal malformations in mice were chronologically observed via 7 T MRI and histology. MR images could be used to distinguish the histological structures of normal and malformed mouse spines. Malformed vertebrae were accompanied by adjacent intervertebral structures that corresponded to the fully segmented structures observed in human congenital scoliosis, but the intervertebral conditions varied. This study suggested the importance of MRI and histological examinations of human congenital scoliosis patients with patterns other than nonsegmenting patterns, which may be used to predict the prognosis of patients with spinal deformities associated with malformed vertebrae.

Whole-body MRI for the investigation of joint involvement in inflammatory arthritis.

OBJECTIVES: This study aimed to develop a novel whole-body MRI protocol capable of assessing inflammatory arthritis at an early stage in multiple joints in one examination. MATERIALS AND METHODS: Forty-six patients with inflammatory joint symptoms and 9 healthy volunteers underwent whole-body MR imaging on a 3.0 T MRI scanner in this prospective study. Image quality and pathology in each joint, bursae, entheses and tendons were scored by two of three radiologists and compared to clinical joint scores. Participants were divided into three groups based on diagnosis at 1-year follow-up (healthy volunteers, rheumatoid arthritis and all other types of arthritis). Radiology scores were compared between the three groups using a Kruskal-Wallis test. The clinical utility of radiology scoring was compared to clinical scoring using ROC analysis. RESULTS: A protocol capable of whole-body MR imaging of the joints with an image acquisition time under 20 min was developed with excellent image quality. Synovitis scores were significantly higher in patients who were diagnosed with rheumatoid arthritis at 12 months (p < 0.05). Radiology scoring of bursitis showed statistically significant differences between each of the three groups-healthy control, rheumatoid arthritis and non-rheumatoid arthritis (p < 0.05). There was no statistically significant difference in ROC analysis between MRI and clinical scores. CONCLUSION: This study has developed a whole-body MRI joint imaging protocol that is clinically feasible and shows good differentiation of joint pathology between healthy controls, patients with rheumatoid arthritis and patients with other forms of arthritis.

Nodular cystic fat necrosis: a distinctive rare soft-tissue mass.

We report the case of a 34-year-old female who was evaluated for a right lower extremity soft-tissue mass, found to be a large cystic lesion bound by fibrous tissue containing innumerable, freely mobile nodules of fat. Her presentation suggested the diagnosis of nodular cystic fat necrosis (NCFN), a rare entity that likely represents a morphological subset of fat necrosis potentially caused by vascular insufficiency secondary to local trauma. Her lesion was best visualized using MRI, which revealed characteristic imaging features of NCFN including nodular lipid-signal foci that suppress on fat-saturated sequences, intralesional fluid with high signal intensity on T2-weighted imaging, and a contrast-enhancing outer capsule with low signal intensity on T1-weighted imaging. Ultrasound imaging offered the advantage of showing mobile hyperechogenic foci within the anechoic cystic structure, and the lesion was otherwise visualized on radiography as a nonspecific soft-tissue radiopacity. She was managed with complete surgical excision with pathologic evaluation demonstrating, similar to the radiologic features, innumerable free-floating, 1-5 mm, smooth, nearly uniform spherical nodules of mature fat with widespread necrosis contained within a thick fibrous pseudocapsule. Follow-up imaging revealed no evidence of remaining or recurrent disease on postoperative follow-up MRI. The differential diagnosis includes lipoma with fat necrosis, lipoma variant, atypical lipomatous tumor, and a Morel-Lavallée lesion. There is overlap in the imaging features between fat necrosis and both benign and malignant adipocytic tumors, occasionally making this distinction based solely on imaging findings challenging. To our knowledge, this is the largest example of NCFN ever reported.

Diagnostic performance and interreader agreement of individual and combined non-enhanced and contrast-enhanced MR imaging parameters in adhesive capsulitis of the shoulder.

OBJECTIVE: The aims of our study were to analyze agreement among readers with different levels of expertise and diagnostic performance of individual and combined imaging signs for the diagnosis of adhesive capsulitis of the shoulder. METHODS: In a retrospective study, contrast-enhanced shoulder MRIs of 60 patients with and 120 without clinically diagnosed adhesive capsulitis were evaluated by three readers independently. As non-enhanced imaging signs, readers evaluated signal intensity and thickness of the axillary recess capsule, thickness of the rotator interval capsule and the coracohumeral ligament as well as obliteration of subcoracoid fat. Furthermore, contrast enhancement of axillary recess and rotator interval capsule were evaluated. Data analysis included interreader reliability, ROC analysis, and logistic regression (p < 0.05). RESULTS: Contrast-enhanced parameters showed substantially higher agreement among readers (ICC 0.79-0.80) than non-enhanced parameters (0.37-0.45). AUCs of contrast-enhanced signs (95.1-96.6%) were significantly higher (p < 0.01) than of non-enhanced imaging signs (61.5-85.9%) when considered individually. Combined evaluation of axillary recess signal intensity and thicknesses of axillary recess or rotator interval-when at least one of two signs was rated positive-increased accuracy compared to individual imaging signs, however not statistically significant. CONCLUSION: Contrast-enhanced imaging signs show both distinctly higher agreement among readers and distinctly higher diagnostic performance compared to non-enhanced imaging signs based on the imaging protocol used in this study. Combined evaluation of parameters showed a tendency to increase discrimination; however, the effect on diagnosis of ACS was not statistically significant.

A comprehensive MRI analysis of osteoid osteomas in patients with diverse radiological features across various regions.

BACKGROUND: Magnetic resonance imaging (MRI), which does not involve ionizing radiation, is the preferred imaging modality for diagnosing osteoid osteoma (OO), an ailment more common in children and young adults. PURPOSE: This study aims to perform a literature review and delineate the MRI findings of OO lesions in patients exhibiting varying radiological features across different regions. MATERIALS AND METHODS: A retrospective study included 63 patients diagnosed with OO through MRI, assessed independently by two blinded radiologists using both standard and dynamic contrast-enhanced MRI techniques. After excluding 7 patients with prior biopsy, surgery, or RFA, the study included 56 patients with 57 lesions. RESULTS: Of 57 lesions evaluated, 50 were in long, and 7 in flat bones. One patient presented with two separate nidi within the intertrochanteric region. Most of the lesions, 49 (86%), were extra-articular, while 8 (14%) were intra-articular. The nidus was intracortical in 45 (78.9%) patients, intramedullary in 5 (8.8%), subperiosteal in 5 (8.8%), and endosteal in 2 (3.5%). Average nidus diameter was 7.02 ± 2.64 mm (3-12.6 mm). Central nidal calcification was present in 68.4% (n = 39) cases. Contrast enhancement was intense at 90.5%, moderate at 9.5%. Reactive sclerosis around the nidus was severe (50.9%), moderate (22.8%), and mild (26.3%). Bone marrow edema was severe (70.2%), moderate (14.0%), and mild (15.8%). Soft tissue edema was identified in 77.2% of all lesions. CONCLUSION: To minimize delays in diagnosis and treatment, radiologists should become acquainted with the typical OO MRI findings and the atypical MRI findings that might be mistaken for other conditions.

MR Imaging of Pediatric Neuroblastoma: Is Gadolinium Enhancement Necessary for Evaluation of Image-Defined-Risk Factors?

Background: Pre-treatment stratification and outcomes of neuroblastoma patients often depend on the assessment of image-defined risk factors (IDRFs) on MR Imaging, usually using Gadolinium-contrast materials which are cautioned in pediatrics. We aimed to address whether gadolinium contrast-enhanced sequences are necessary to identify the presence/absence of IDRFs. Methods: Patients with neuroblastoma with MR imaging were retrospectively identified from 2005 to 2021. Ninety confirmed IDRFs were evaluated in 23 patients. Corresponding MR studies were anonymized, randomized, and independently evaluated by 3 fellowship-trained pediatric radiologists. Each radiologist assessed the studies twice. At the first reading, all enhanced sequences were omitted, while in the second reading, the full study with enhanced sequences were included. Consensus reading was obtained among readers. Inter- and intra-rater agreements using Kappa statistics (κ) as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of non-enhanced MR in assessing IDRFs with respect to enhanced MR were calculated. Results: There were substantial (ĸ: 0.64-0.73) intra-reader agreements, and moderate to substantial (ĸ: 0.57-0.62) inter-reader agreements among radiologists in identifying IDRFs using non-enhanced MR. Non-enhanced MR had a sensitivity of 87.8% (95% CI [79-94]), specificity of 93% (89-96), PPV of 82.3 (73-89), NPV of 95.4 (92-98), and accuracy of 91.6 (88-94) in identifying IDRFs. However, 5/23 patients (21.7%) had a change in staging with the inclusion of contrast sequences. Conclusion: Although contrast sequences have a role in IDRF assessment, the majority can be adequately assessed on MR without gadolinium-contrast enhancement. Validation in a larger cohort is an important next step.

[Analysis of intracranial saccular aneurysm wall: neuroimaging and histopathological correlates]. / Issledovanie stenki intrakranial'nykh meshotchatykh anevrizm: neirovizualizatsionnye i gistopatologicheskie korrelyaty.

BACKGROUND: Contrast enhancement of intracranial aneurysm wall during MRI with targeted visualization of vascular wall correlates with previous aneurysm rupture and, according to some data, may be a predictor of further rupture of unruptured aneurysms. OBJECTIVE: To analyze possible causes of aneurysm contrast enhancement considering morphological data of aneurysm walls. MATERIAL AND METHODS: The study included 44 patients with intracranial aneurysms who underwent preoperative MRI between November 2020 and September 2022. Each aneurysm was assessed regarding contrast enhancement pattern. Microsurgical treatment of aneurysm was accompanied by resection of its wall for subsequent histological and immunohistochemical analysis regarding thrombosis, inflammation and neovascularization. Specimens were subjected to histological and immunochemical analysis. Immunohistochemical analysis was valuable to estimate inflammatory markers CD68 and CD3, as well as neurovascularization marker SD31. RESULTS: Aneurysms with contrast-enhanced walls were characterized by higher number of CD3+, CD68+, CD31+ cells and parietal clots. Intensity of contrast enhancement correlated with aneurysm wall abnormalities. CONCLUSION: Contrast enhancement of aneurysm wall can characterize various morphological abnormalities.

Inhomogeneous Magnetization Transfer (ihMT) imaging in the acute cuprizone mouse model of demyelination/remyelination.

BACKGROUND: To investigate the association of ihMT (inhom signals with the demyelination and remyelination phases of the acute cuprizone mouse model in comparison with histology, and to assess the extent of tissue damage and repair from MRI data. METHODS: Acute demyelination by feeding 0.2% cuprizone for five weeks, followed by a four-week remyelination period was applied on genetically modified plp-GFP mice. Animals were scanned at different time points of the demyelination and remyelination phases of the cuprizone model using a multimodal MRI protocol, including ihMT T1D-filters, MPF (Macromolecular Proton Fraction) and R1 (longitudinal relaxation rate). For histology, plp-GFP (proteolipid protein - Green Fluorescent Protein) microscopy and LFB (Luxol Fast Blue) staining were employed as references for the myelin content. Comparison of MRI with histology was performed in the medial corpus callosum (mCC) and cerebral cortex (CTX) at two brain levels whereas ROI-wise and voxel-based analyses of the MRI metrics allowed investigating in vivo the spatial extent of myelin alterations. RESULTS: IhMT high-pass T1D-filters, targeted toward long T1D components, showed significant temporal variations in the mCC consistent with the effects induced by the cuprizone toxin. In addition, the corresponding signals correlated strongly and significantly with the myelin content assessed by GFP fluorescence and LFB staining over the demyelination and the remyelination phases. The signal of the band-pass T1D-filter, which isolates short T1D components, showed changes over time that were poorly correlated with histology, hence suggesting a sensitivity to pathological processes possibly not related to myelin. Although MPF was also highly correlated to histology, ihMT high-pass T1D-filters showed better capability to characterize the spatial-temporal patterns during the demyelination and remyelination phases of the acute cuprizone model (e.g., rostro-caudal gradient of demyelination in the mCC previously described in the literature). CONCLUSIONS: IhMT sequences selective for long T1D components are specific and sensitive in vivo markers of demyelination and remyelination and have successfully captured the spatially heterogeneous pattern of the demyelination and remyelination mechanisms in the cuprizone model. Interestingly, differences in signal variations between the ihMT high-pass and band-pass T1D-filter, suggest a sensitivity of the ihMT sequences targeted to short T1Ds to alterations other than those of myelin. Future studies will need to further address these differences by examining more closely the origin of the short T1D components and the variation of each T1D component in pathology.

T1 and FLAIR signal intensities are related to tau pathology in dominantly inherited Alzheimer disease.

Carriers of mutations responsible for dominantly inherited Alzheimer disease provide a unique opportunity to study potential imaging biomarkers. Biomarkers based on routinely acquired clinical MR images, could supplement the extant invasive or logistically challenging) biomarker studies. We used 1104 longitudinal MR, 324 amyloid beta, and 87 tau positron emission tomography imaging sessions from 525 participants enrolled in the Dominantly Inherited Alzheimer Network Observational Study to extract novel imaging metrics representing the mean (µ) and standard deviation (σ) of standardized image intensities of T1-weighted and Fluid attenuated inversion recovery (FLAIR) MR scans. There was an exponential decrease in FLAIR-µ in mutation carriers and an increase in FLAIR and T1 signal heterogeneity (T1-σ and FLAIR-σ) as participants approached the symptom onset in both supramarginal, the right postcentral and right superior temporal gyri as well as both caudate nuclei, putamina, thalami, and amygdalae. After controlling for the effect of regional atrophy, FLAIR-µ decreased and T1-σ and FLAIR-σ increased with increasing amyloid beta and tau deposition in numerous cortical regions. In symptomatic mutation carriers and independent of the effect of regional atrophy, tau pathology demonstrated a stronger relationship with image intensity metrics, compared with amyloid pathology. We propose novel MR imaging intensity-based metrics using standard clinical T1 and FLAIR images which strongly associates with the progression of pathology in dominantly inherited Alzheimer disease. We suggest that tau pathology may be a key driver of the observed changes in this cohort of patients.

Validation of multiparametric MRI based prediction model in identification of pseudoprogression in glioblastomas.

BACKGROUND: Accurate differentiation of pseudoprogression (PsP) from tumor progression (TP) in glioblastomas (GBMs) is essential for appropriate clinical management and prognostication of these patients. In the present study, we sought to validate the findings of our previously developed multiparametric MRI model in a new cohort of GBM patients treated with standard therapy in identifying PsP cases. METHODS: Fifty-six GBM patients demonstrating enhancing lesions within 6 months after completion of concurrent chemo-radiotherapy (CCRT) underwent anatomical imaging, diffusion and perfusion MRI on a 3 T magnet. Subsequently, patients were classified as TP + mixed tumor (n = 37) and PsP (n = 19). When tumor specimens were available from repeat surgery, histopathologic findings were used to identify TP + mixed tumor (> 25% malignant features; n = 34) or PsP (< 25% malignant features; n = 16). In case of non-availability of tumor specimens, ≥ 2 consecutive conventional MRIs using mRANO criteria were used to determine TP + mixed tumor (n = 3) or PsP (n = 3). The multiparametric MRI-based prediction model consisted of predictive probabilities (PP) of tumor progression computed from diffusion and perfusion MRI derived parameters from contrast enhancing regions. In the next step, PP values were used to characterize each lesion as PsP or TP+ mixed tumor. The lesions were considered as PsP if the PP value was < 50% and TP+ mixed tumor if the PP value was ≥ 50%. Pearson test was used to determine the concordance correlation coefficient between PP values and histopathology/mRANO criteria. The area under ROC curve (AUC) was used as a quantitative measure for assessing the discriminatory accuracy of the prediction model in identifying PsP and TP+ mixed tumor. RESULTS: Multiparametric MRI model correctly predicted PsP in 95% (18/19) and TP+ mixed tumor in 57% of cases (21/37) with an overall concordance rate of 70% (39/56) with final diagnosis as determined by histopathology/mRANO criteria. There was a significant concordant correlation coefficient between PP values and histopathology/mRANO criteria (r = 0.56; p < 0.001). The ROC analyses revealed an accuracy of 75.7% in distinguishing PsP from TP+ mixed tumor. Leave-one-out cross-validation test revealed that 73.2% of cases were correctly classified as PsP and TP + mixed tumor. CONCLUSIONS: Our multiparametric MRI based prediction model may be helpful in identifying PsP in GBM patients.