MRI Mapping Research Articles

Unipolar electroanatomical mapping outperforms bipolar voltage in detecting LGE areas in the left atrium

Abstract Introduction In atrial fibrillation (AF) management, understanding left atrial substrate is crucial. While both electroanatomical mapping (EAM) and late gadolinium enhancement MRI (LGE MRI) are reliable methods in assessing atrial substrate and are associated with the ablation outcome, recent findings have highlighted significant discrepancies between bipolar low voltage areas (LVA) in EAM and LGE areas. Objective Explore the relationship between LGE areas and unipolar LVAs by utilizing multipolar high-density (HD) mapping. Methods Nineteen patients scheduled for AF ablation underwent pre-ablation LGE-MRI. Left atrial (LA) segmentation was conducted using a convolutional neural network, which subsequently generated a 3D mesh integrating the LGE data. HD-EAM was performed in sinus rhythm for each patient, capturing at least 4000 points. The EAM map and LGE MRI mesh were co-registered. LVA areas were defined using voltage cut-offs of 0.5 mV for bipolar and 2.5 mV for unipolar measurements. Correspondence between LGE areas and LVAs on the anterior and posterior LA wall was analyzed. Results Both bipolar and unipolar LVA demonstrated high precision in detecting LGE areas (100% and 88% respectively). However, unipolar LVA exhibited a remarkable accuracy of 81% for detecting LGE areas specifically, whereas bipolar LVA displayed a significantly lower accuracy of 28%. These findings were consistent across the different atrial walls. Conclusion Incorporating unipolar voltage data into electroanatomical mapping in the atrium may bridge the observed gap between LGE areas and bipolar LVAs. Our findings highlight the significance of unipolar voltage in evaluating the left atrial substrate, potentially offering a more comprehensive insight into the different layers of atrial walls, and opening the door for new approaches in AF therapy.

ANALYZING THE RELATIONSHIP AMONG CLINICAL SYMPTOMS, X-RAY RESULTS, AND CARTILAGE WEAR PATTERNS IN KNEE OSTEOARTHRITIS USING T2 MAPPING MRI

Objectives: Osteoarthritis (OA) is a condition that causes joint pain, varying degrees of functional limitations, and a decrease in overall quality of life. The purpose of this study was to examine the progression of cartilage degeneration in knees affected by symptomatic OA and determine its relationship with X-ray and T2 map MRI findings. Methods: This study was conducted at a Tertiary Care Teaching Institute in India and involved 40 patients. It was an observational type of study. For our assessment, we utilized the Western Ontario and McMaster University (WOMAC) osteoarthrosis index to evaluate function, quality of life, and joint pain. Medical imaging technique A standing AP view of the affected knee joint was taken using plain radiographs. Once the X-rays were obtained, they were graded using the Kellgren–Lawrence Classification, which ranges from 0 to 4 grades. Results: Out of the total patients, 6.0% were <40 years old, 21.2% were between 41 and 50 years old, 27.2% were between 51 and 60 years old, 39.3% were between 61 and 70 years old, and 6.0% were above 70 years old. In this study, there were 21 females (63.6%) and 12 males (36.4%). In this study, the researchers found that there was no distinction between the sides of the limb affected. Both the left and right sides were involved in 13 cases each, accounting for 39.39% of the total cases. In addition, 7 cases, or 21.21%, reported experiencing bilateral knee pain. Merchant grade reported that out of the knees examined, 17.5% had Grade 0, 45% had Grade 1, 27.5% had Grade 2, 10% had Grade 3, and none had Grade 4. Conclusion: The findings of this study suggest that T2 map MRI has the ability to accurately measure abnormal cartilage changes in conditions that affect the mechanical properties of the knee joint. It is crucial to have non-invasive methods that can assess early cartilage matrix changes. These methods are important for initiating early treatment, monitoring disease progression, planning operative procedures, and following up on operative cartilage repair.

Impact of paramagnetic rim lesions on disability and race in multiple sclerosis: mediation analysis.

Black American (BA) multiple sclerosis (MS) patients experience greater disability compared to White American (WA) patients. Here, we investigated the role of paramagnetic rim lesions (PRLs), a subset of chronic active lesions, on race-related disability in MS. We conducted a retrospective observational study comparing BA and WA MS patients. PRLs were identified through Quantitative Susceptibility Mapping (QSM) MRI. A causal mediation analysis explored the impact of PRLs on the relationship between race and disability, as measured by the Expanded Disability Status Scale (EDSS). The prevalence of PRLs in BA patients with MS was higher at 55% compared to WA patients at 39% (p = 0.022). A higher percentage of PRLs among all white matter lesions was observed with BA (8.01%) patients compared to WA (3.4%) patients (p = 0.003). In a regression analysis, controlling for significant patient-level covariates and income-level demographics, the percentage of PRLs was, on average, 4.61 points higher for BA patients than for WA patients (p = 0.003). In a separate regression analysis, accounting for covariates, BA patients exhibited significantly higher EDSS scores (p < 0.001). Further analysis demonstrated that the percentage of PRLs was a mediator in the association between BA patients and greater disability (p = 0.031). Higher proportion of PRLs in BA population accounted for 14% of the total effect of race on disability. BA patients exhibit greater disability, in part, due to their higher proportion of PRLs. This study underscores the substantial impact of chronic active lesions on disability outcomes in this specific minority MS patient population.

The role of variation in phonological and semantic working memory capacities in sentence comprehension: neural evidence from healthy and brain-damaged individuals.

Research on the role of working memory (WM) in language processing has typically focused on WM for phonological information. However, considerable behavioral evidence supports the existence of a separate semantic WM system that plays a greater role in language processing. We review the neural evidence that supports the distinction between phonological and semantic WM capacities and discuss how individual differences in these capacities relate to sentence processing. In terms of neural substrates, findings from multivariate functional MRI for healthy participants and voxel-based lesion-symptom mapping for brain-damaged participants imply that the left supramarginal gyrus supports phonological WM, whereas the left inferior frontal gyrus (LIFG) and angular gyrus support semantic WM. In sentence comprehension, individual variation in semantic but not phonological WM related to performance in resolving semantic information and the LIFG region implicated in semantic WM showed fMRI activation during the resolution of semantic interference. Moreover, variation for brain-damaged participants in the integrity of a fiber tract supporting semantic WM had a greater relation to the processing of complex sentences than did the integrity of fiber tracts supporting phonological WM. Overall, the neural findings provide converging evidence regarding the distinction of these two capacities and the greater contribution of individual differences in semantic than phonological WM capacity to sentence processing.

Dynamic Contrast Enhanced MRI Mapping of Vascular Permeability for Evaluation of Breast Cancer Neoadjuvant Chemotherapy Response Using Image-to-Image Conditional Generative Adversarial Networks.

Dynamic contrast enhanced (DCE) MRI is a non-invasive imaging technique that has become a quantitative standard for assessing tumor microvascular permeability. Through the application of a pharmacokinetic (PK) model to a series of T1-weighed MR images acquired after an injection of a contrast agent, several vascular permeability parameters can be quantitatively estimated. These parameters, including Ktrans, a measure of capillary permeability, have been widely implemented for assessing tumor vascular function as well as tumor therapeutic response. However, conventional PK modeling for translation of DCE MRI to PK vascular permeability parameter maps is complex and time-consuming for dynamic scans with thousands of pixels per image. In recent years, image-to-image conditional generative adversarial network (cGAN) is emerging as a robust approach in computer vision for complex cross-domain translation tasks. Through a sophisticated adversarial training process between two neural networks, image-to-image cGANs learn to effectively translate images from one domain to another, producing images that are indistinguishable from those in the target domain. In the present study, we have developed a novel image-to-image cGAN approach for mapping DCE MRI data to PK vascular permeability parameter maps. The DCE-to-PK cGAN not only generates high-quality parameter maps that closely resemble the ground truth, but also significantly reduces computation time over 1000-fold. The utility of the cGAN approach to map vascular permeability is validated using open-source breast cancer patient DCE MRI data provided by The Cancer Imaging Archive (TCIA). This data collection includes images and pathological analyses of breast cancer patients acquired before and after the first cycle of neoadjuvant chemotherapy (NACT). Importantly, in good agreement with previous studies leveraging this dataset, the percentage change of vascular permeability Ktrans derived from the DCE-to-PK cGAN enables early prediction of responders to NACT.

Focused Ultrasound Impels the Delivery and Penetration of Model Therapeutics into Cerebral Cavernous Malformations.

Cerebral cavernous malformations (CCMs) are vascular neoplasms in the brain that can cause debilitating symptoms. Current treatments pose significant risks to some patients, motivating the development of new nonsurgical options. We recently discovered that focused ultrasound-mediated blood-brain barrier opening (FUS) arrests CCM formation and growth. Here, we build on this discovery and assess the ability of FUS to deliver model therapeutics into CCMs. Quantitative T1 mapping MRI sequences were used with 1 kDa (MultiHance; MH) and 17 kDa (GadoSpin D; GDS) contrast agents to assess the FUS-mediated delivery and penetration of model small molecule drugs and biologics, respectively, into CCMs of Krit1 mutant mice. FUS elevated the rate of MH delivery to both the lesion core (4.6-fold) and perilesional space (6.7-fold). Total MH delivery more than doubled in the lesion core and tripled in the perilesional space when FUS was applied immediately prior to MH injection. For the model biologic drug (i.e. GDS), FUS was of greater relative benefit, resulting in 21.7-fold and 3.8-fold delivery increases to the intralesional and perilesional spaces, respectively. FUS is capable of impelling the delivery and penetration of therapeutics into the complex and disorganized CCM microenvironment. Benefits to small molecule drug delivery are more evident in the perilesional space, while benefits to biologic delivery are more evident in CCM cores. These findings, when combined with ability of FUS alone to control CCMs, highlight the potential of FUS to serve as a powerful non-invasive therapeutic platform for CCM.

Iron changes within infarct tissue in ischemic stroke patients after successful reperfusion quantified using QSM.

For nearly half of patients who undergo Endovascular Thrombectomy following ischemic stroke, successful recanalisation does not guarantee a good outcome. Understanding the underlying tissue changes in the infarct tissue with the help of biomarkers specific to ischemic stroke could offer valuable insights for better treatment and patient management decisions. Using quantitative susceptibility mapping (QSM) MRI to measure cerebral iron concentration, this study aims to track the progression of iron within the infarct lesion after successful reperfusion. In a prospective study of 87 ischemic stroke patients, successfully reperfused patients underwent MRI scans at 24-to-72h and 3 months after reperfusion. QSM maps were generated from gradient-echo MRI images. QSM values, measured in parts per billion (ppb), were extracted from ROIs defining the infarct and mirror homolog in the contralateral hemisphere and were compared cross-sectionally and longitudinally. QSM values in the infarct ROIs matched those of the contralateral ROIs at 24-to-72h, expressed as median (interquartile range) ppb [0.71(-7.67-10.09) vs. 2.20(-10.50-14.05) ppb, p = 0.55], but were higher at 3 months [10.68(-2.30-21.10) vs. -1.27(-12.98-9.82) ppb, p < 0.001]. The infarct QSM values at 3 months were significantly higher than those at 24-to-72h [10.41(-2.50-18.27) ppb vs. 1.68(-10.36-12.25) ppb, p < 0.001]. Infarct QSM at 24-to-72h and patient outcome measured at three months did not demonstrate a significant association. Following successful endovascular reperfusion, iron concentration in infarct tissue, as measured by QSM increases over time compared to that in healthy tissue. However, its significance warrants further investigation.

Optimization and validation of low-field MP2RAGE T1 mapping on 0.35T MR-Linac: Toward adaptive dose painting with hypoxia biomarkers.

Stereotactic MR-guided Adaptive Radiation Therapy (SMART) dose painting for hypoxia has potential to improve treatment outcomes, but clinical implementation on low-field MR-Linac faces substantial challenges due to dramatically lower signal-to-noise ratio (SNR) characteristics. While quantitative MRI and T1 mapping of hypoxia biomarkers show promise, T1-to-noise ratio (T1NR) optimization at low fields is paramount, particularly for the clinical implementation of oxygen-enhanced (OE)-MRI. The 3D Magnetization Prepared (2) Rapid Gradient Echo (MP2RAGE) sequence stands out for its ability to acquire homogeneous T1-weighted contrast images with simultaneous T1 mapping. To optimize MP2RAGE for low-field T1 mapping; conduct experimental validation in a ground-truth phantom; establish feasibility and reproducibility of low-field MP2RAGE acquisition and T1 mapping in healthy volunteers. The MP2RAGE optimization was performed to maximize the contrast-to-noise ratio (CNR) of T1 values in white matter (WM) and gray matter (GM) brain tissues at 0.35T. Low-field MP2RAGE images were acquired on a 0.35T MR-Linac (ViewRay MRIdian) using a multi-channel head coil. Validation of T1 mapping was performed with a ground-truth Eurospin phantom, containing inserts of known T1 values (400-850ms), with one and two average (1A and 2A) MP2RAGE scans across four acquisition sessions, resulting in eight T1 maps. Mean (±SD) T1 relative error, T1NR, and intersession coefficient of variation (CV) were determined. Whole-brain MP2RAGE scans were acquired in 5 healthy volunteers across two sessions (A and B) and T1 maps were generated. Mean (±SD) T1 values for WM and GM were determined. Whole-brain T1 histogram analysis was performed, and reproducibility was determined with the CV between sessions. Voxel-by-voxel T1 difference maps were generated to evaluate 3D spatial variation. Low-field MP2RAGE optimization resulted in parameters: MP2RAGETR of 3250ms, inversion times (TI1/TI2) of 500/1200ms, and flip angles (α1/α2) of 7/5°. Eurospin T1 maps exhibited a mean (±SD) relative error of 3.45%±1.30%, T1NR of 20.13±5.31, and CV of 2.22%±0.67% across all inserts. Whole-brain MP2RAGE images showed high anatomical quality with clear tissue differentiation, resulting in mean (±SD) T1 values: 435.36±10.01ms for WM and 623.29±14.64ms for GM across subjects, showing excellent concordance with literature. Whole-brain T1 histograms showed high intrapatient and intersession reproducibility with characteristic intensity peaks consistent with voxel-level WM and GM T1 values. Reproducibility analysis revealed a CV of 0.46%±0.31% and 0.35%±0.18% for WM and GM, respectively. Voxel-by-voxel T1 difference maps show a normal 3D spatial distribution of noise in WM and GM. Low-field MP2RAGE proved effective in generating accurate, reliable, and reproducible T1 maps with high T1NR in phantom studies and in vivo feasibility established in healthy volunteers. While current work is focused on refining the MP2RAGE protocol to enable clinically efficient OE-MRI, this study establishes a foundation for TOLD T1 mapping for hypoxia biomarkers. This advancement holds the potential to facilitate a paradigm shift toward MR-guided biological adaptation and dose painting by leveraging 3D hypoxic spatial distributions and improving outcomes in conventionally challenging-to-treat cancers.

Development and performance evaluation of fully automated deep learning-based models for myocardial segmentation on T1 mapping MRI data

To develop a deep learning-based model capable of segmenting the left ventricular (LV) myocardium on native T1 maps from cardiac MRI in both long-axis and short-axis orientations. Models were trained on native myocardial T1 maps from 50 healthy volunteers and 75 patients using manual segmentation as the reference standard. Based on a U-Net architecture, we systematically optimized the model design using two different training metrics (Sørensen-Dice coefficient = DSC and Intersection-over-Union = IOU), two different activation functions (ReLU and LeakyReLU) and various numbers of training epochs. Training with DSC metric and a ReLU activation function over 35 epochs achieved the highest overall performance (mean error in T1 10.6 ± 17.9 ms, mean DSC 0.88 ± 0.07). Limits of agreement between model results and ground truth were from -35.5 to + 36.1 ms. This was superior to the agreement between two human raters (-34.7 to + 59.1 ms). Segmentation was as accurate for long-axis views (mean error T1: 6.77 ± 8.3 ms, mean DSC: 0.89 ± 0.03) as for short-axis images (mean error ΔT1: 11.6 ± 19.7 ms, mean DSC: 0.88 ± 0.08). Fully automated segmentation and quantitative analysis of native myocardial T1 maps is possible in both long-axis and short-axis orientations with very high accuracy.

Associations of Cerebral Blood Flow Patterns With Gray and White Matter Structure in Patients With Temporal Lobe Epilepsy.

Neuroimaging studies in patients with temporal lobe epilepsy (TLE) show widespread brain network alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. Here, we studied whole-brain perfusion and vascular network alterations in TLE and assessed its associations with gray and white matter compromises and various clinical variables. We included individuals with and without pharmaco-resistant TLE who underwent multimodal 3T MRI, including arterial spin labelling, structural, and diffusion-weighted imaging. Using surface-based MRI mapping, we generated individualized cortico-subcortical profiles of perfusion, morphology, and microstructure. Linear models compared regional CBF in patients with controls and related alterations to morphological and microstructural metrics. We further probed interregional vascular networks in TLE, using graph theoretical CBF covariance analysis. The effects of disease duration were explored to better understand the progressive changes in perfusion. We assessed the utility of perfusion in separating patients with TLE from controls using supervised machine learning. Compared with control participants (n = 38; mean ± SD age 34.8 ± 9.3 years; 20 females), patients with TLE (n = 24; mean ± SD age 35.8 ± 10.6 years; 12 females) showed widespread CBF reductions predominantly in fronto-temporal regions (Cohen d -0.69, 95% CI -1.21 to -0.16), consistent in a subgroup of patients who remained seizure-free after surgical resection of the seizure focus. Parallel structural profiling and network-based models showed that cerebral hypoperfusion may be partially constrained by gray and white matter changes (8.11% reduction in Cohen d) and topologically segregated from whole-brain perfusion networks (area under the curve -0.17, p < 0.05). Negative effects of progressive disease duration further targeted regional CBF profiles in patients (r = -0.54, 95% CI -0.77 to -0.16). Perfusion-derived classifiers discriminated patients from controls with high accuracy (71% [70%-82%]). Findings were robust when controlling for several methodological confounds. Our multimodal findings provide insights into vascular contributions to TLE pathophysiology affecting and extending beyond mesiotemporal structures and highlight their clinical potential in epilepsy diagnosis. As our work was cross-sectional and based on a single site, it motivates future longitudinal studies to confirm progressive effects, ideally in a multicentric setting.

Advances in the diagnosis of multiorgan involvement in systemic sclerosis: a focus on MRI.

Systemic sclerosis (SSc) is a rare chronic multisystem autoimmune disease characterized by endothelial dysfunction, tissue hypoxia, and diffuse organ fibrosis. MRI provides a radiation free approach to noninvasively assess the key manifestations of SSc in multiple organs. The purpose of this review is to summarize recent advances in MRI techniques to provide diagnostic and prognostic information in patients with SSc. MRI can probe processes that play a key role in the development of SSc-related complications, including neointima proliferation, fibrosis, and hypoxia. Feature tracking and parametric mapping MRI can detect cardiac involvement at the subclinical level. Contrast-free MRI angiography with Digital Artery Volume Index (DAVIX) assessment allow comprehensive assessment of hand involvement. T1 mapping and BOLD imaging can assess SSc effects on skeletal muscle, and lung MRI is becoming a key method for imaging of interstitial lung disease. As a new exciting application, the sodium content of the skin can be quantified by 23Na MRI reflective of glycosaminoglycan content. Recent advances in MRI provide a unique opportunity to study the key pathophysiologic processes and clinical manifestations of SSc in multiple organs noninvasively, which can pave the way for the development of effective therapies.

Temporal dynamics of white and gray matter plasticity during motor skill acquisition: a comparative diffusion tensor imaging and multiparametric mapping analysis.

Learning new motor skills relies on neural plasticity within motor and limbic systems. This study uniquely combined diffusion tensor imaging and multiparametric mapping MRI to detail these neuroplasticity processes. We recruited 18 healthy male participants who underwent 960min of training on a computer-based motion game, while 14 were scanned without training. Diffusion tensor imaging, which quantifies tissue microstructure by measuring the capacity for, and directionality of, water diffusion, revealed mostly linear changes in white matter across the corticospinal-cerebellar-thalamo-hippocampal circuit. These changes related to performance and reflected different responses to upper- and lower-limb training in brain areas with known somatotopic representations. Conversely, quantitative MRI metrics, sensitive to myelination and iron content, demonstrated mostly quadratic changes in gray matter related to performance and reflecting somatotopic representations within the same brain areas. Furthermore, while myelin and iron-sensitive multiparametric mapping MRI was able to describe time lags between different cortical brain systems, diffusion tensor imaging detected time lags within the white matter of the motor systems. These findings suggest that motor skill learning involves distinct phases of white and gray matter plasticity across the sensorimotor network, with the unique combination of diffusion tensor imaging and multiparametric mapping MRI providing complementary insights into the underlying neuroplastic responses.

Quantitative transport mapping of multi-delay arterial spin labeling MRI detects early blood perfusion alterations in Alzheimer’s disease

BackgroundQuantitative transport mapping (QTM) of blood velocity, based on the transport equation has been demonstrated higher accuracy and sensitivity of perfusion quantification than the traditional Kety’s method-based cerebral blood flow (CBF). This study aimed to investigate the associations between QTM velocity and cognitive function in Alzheimer’s disease (AD) using multiple post-labeling delay arterial spin labeling (ASL) MRI.MethodsA total of 128 subjects (21 normal controls (NC), 80 patients with mild cognitive impairment (MCI), and 27 AD) were recruited prospectively. All participants underwent MRI examination and neuropsychological evaluation. QTM velocity and traditional CBF maps were computed from multiple delay ASL. Regional quantitative perfusion measurements were performed and compared to study group differences. We tested the hypothesis that cognition declines with reduced cerebral blood perfusion with consideration of age and gender effects.ResultsIn cortical gray matter (GM) and the hippocampus, QTM velocity and CBF showed decreased values in the AD group compared to NC and MCI groups; QTM velocity, but not CBF, showed a significant difference between MCI and NC groups. QTM velocity and CBF showed values decreasing with age; QTM velocity, but not CBF, showed a significant gender difference between male and female. QTM velocity and CBF in the hippocampus were positively correlated with cognition, including global cognition, memory, executive function, and language function.ConclusionThis study demonstrated an increased sensitivity of QTM velocity as compared with the traditional Kety’s method-based CBF. Specifically, we observed only in QTM velocity, reduced perfusion velocity in GM and the hippocampus in MCI compared with NC. Both QTM velocity and CBF demonstrated a reduction in AD vs. controls. Decreased QTM velocity and CBF in the hippocampus were correlated with poor cognitive measures. These findings suggest QTM velocity as potential biomarker for early AD blood perfusion alterations and it could provide an avenue for early intervention of AD.

(005) MRI TECHNIQUES FOR IMAGING BIOMARKERS OF RADIATION-INDUCED DAMAGE TO FEMALE ERECTILE TISSUES AND OTHER GENITOPELVIC ORGANS

Abstract Introduction Difficulties with arousal and orgasm are common in female patients after pelvic radiation. Yet, current classifications of toxicity and normal tissues in radiation oncology account poorly for the anatomy and critical function of female erectile tissues (arousal and orgasm) with respect to patients’ capacities to continue to engage in pleasurable sexual behaviors after cancer treatment. MRI imaging biomarkers of dose-volume dependent radiation damage can provide objective measures of the impact of interventions, help predict sexual dysfunction, and allow for re-optimization of therapy for early mitigation of radiation damage to female erectile tissues. Objective The aim of this project is to develop and optimize MRI imaging techniques for female erectile tissues and other genitopelvic organs. Optimization of this MRI protocol will allow us to establish quantitative and qualitative indices of radiation damage to specific sexual organs, providing mechanistic insights into how to measure radiation damage of current and future therapies. Methods This prospective study includes two female-identifying volunteers with healthy female pelvic anatomy who underwent MRI scans using a 3.0T MRI (Prisma, Siemens Healthcare) scanner. The protocol (Table 1) included 2D T2-weighted turbo spin-echo (TSE) sequences in the axial (spatial resolution 0.5x0.5x2mm), coronal (spatial resolution 0.5x0.5x3mm), and sagittal planes (spatial resolution 0.3x0.3x2mm), T2-weighted with fat saturation in the axial plane (spatial resolution: 0.8x0.8x4mm) diffusion-weighted tensor imaging (DTI, axial plane with 30 diffusion directions and b-values 0s/mm2 and 400s/mm2, TR/TE: 3000/57ms, spatial resolution 1.3x1.3x5mm). Protocol optimization in healthy volunteers consisted of imaging without gadolinium contrast, while future imaging in patients will also include dynamic contrast-enhanced MRI (3D T1-weighted radial acquisition in the axial plane, with 4.7s temporal resolution, 20 slices, spatial resolution 0.8x0.8x2mm) and T1 mapping (axial plane variable flip angle, B1-corrected acquisition with 5 flip angles: 5, 10, 15, 20, 30 degrees, TR/TE: 5.9/2.4ms, with 0.8x0.8x2mm spatial resolution). The sexual regions of interest (ROIs) included the female external genitalia, vagina, bulboclitoris (clitoris and vestibular bulbs), pelvic neurovasculature, and pelvic floor muscles which were visualized and contoured per standard protocols. Results The axial T2-weighted TSE sequences in 2mm slices provided clear visualization of the female erectile tissues for contouring the bulboclitoris, vaginal canal, and external genitalia (Figure 1). The T2-weighted sequences with fat saturation allows us to conduct MR neurography to evaluate the three-dimensional visibility of the nerves (plexus, pudendal and cavernous), enabling us to localize and characterize nerve abnormalities with dose-dependent radiation damage (Figure 2). Perfusion time intensity curves created with the T1 DCE scans can assess changes in vasculature, and the initial areas under the time to signal intensity curve (IAUC) will act as biomarkers for erectile tissue perfusion and permeability. Additional biomarkers include ROI intensity and volume/thickness for both erectile tissues and the vagina wall, as well as fractional anisotropy for the vagina alone. Lastly, we explore the clinical applications of DTI with fiber tractography to evaluate pelvic floor musculature. Conclusions These MRI techniques will be the first to validate normal tissue toxicity imaging biomarkers for radiation damage, allowing us to objectively measure dose-dependent inflammatory, fibrotic and vasculogenic effects of radiotherapy. Disclosure No.

Differential Diagnosis of Prostate Cancer Grade to Augment Clinical Diagnosis Based on Classifier Models with Tuned Hyperparameters.

We developed a novel machine-learning algorithm to augment the clinical diagnosis of prostate cancer utilizing first and second-order texture analysis metrics in a novel application of machine-learning radiomics analysis. We successfully discriminated between significant prostate cancers versus non-tumor regions and provided accurate prediction between Gleason score cohorts with statistical sensitivity of 0.82, 0.81 and 0.91 in three separate pathology classifications. Tumor heterogeneity and prediction of the Gleason score were quantified using two feature selection approaches and two separate classifiers with tuned hyperparameters. There was a total of 71 patients analyzed in this study. Multiparametric MRI, incorporating T2WI and ADC maps, were used to derive radiomics features. Recursive feature elimination (RFE), the least absolute shrinkage and selection operator (LASSO), and two classification approaches, incorporating a support vector machine (SVM) (with randomized search) and random forest (RF) (with grid search), were utilized to differentiate between non-tumor regions and significant cancer while also predicting the Gleason score. In T2WI images, the RFE feature selection approach combined with RF and SVM classifiers outperformed LASSO with SVM and RF classifiers. The best performance was achieved by combining LASSO and SVM into a model that used both T2WI and ADC images. This model had an area under the curve (AUC) of 0.91. Radiomic features computed from ADC and T2WI images were used to predict three groups of Gleason score using two kinds of feature selection methods (RFE and LASSO), RF and SVM classifier models with tuned hyperparameters. Using combined sequences (T2WI and ADC map images) and combined radiomics (1st and GLCM features), LASSO, with a feature selection method with RF, was able to predict G3 with the highest sensitivity at a level AUC of 0.92. To predict G3 for single sequence (T2WI images) using GLCM features, LASSO with SVM achieved the highest sensitivity with an AUC of 0.92.

Loose Seton Technique in the Management of Complex High Anal Fistula: Enhancing Outcomes with Magnetic Resonance Imaging

Background: Complex high anal fistulas challenge treatment efforts, necessitating innovative approaches that balance healing with sphincter preservation. Methods and Results: In a prospective study at Tikrit Teaching Hospital, 39 patients with complex high anal fistulas underwent treatment with loose silicone setons, guided by preoperative MRI mapping. The efficacy of this method was evaluated through follow-up visits at 1, 3, and 6 months, focusing on fistula healing, recurrence rates, continence preservation (assessed by the Wexner Continence Score), and patient satisfaction. Complete healing was achieved in 31 patients (79.5%), with a recurrence rate of 7.7%. There was a significant improvement in continence, with the mean Wexner score reducing from 3.5 to 1.2 (P&lt;0.001). Moreover, 85% of patients expressed satisfaction with their treatment outcomes. Conclusion: The combined use of loose silicone setons and MRI mapping presents an effective, satisfactory method for managing complex high anal fistulas. This technique ensures high healing rates, significantly preserves sphincter function, and achieves high patient satisfaction.

A novel MRI-based tumor-targeting theragnostic agent: Magnetoelectric nanoparticles in an in vivo murine KRAS/P53 pancreatic flank tumor model.

3075 Background: Magnetoelectric nanoparticles (MENPs) are a novel material with a magnetoelectric (ME) property that allows for conversion of an external magnetic field to a local electric field (EF) that can be exploited to generate a Coulomb force to target and electroporate the relatively non-polarized tumor cell walls. We hypothesized that their local EF and superparamagnetic cores can be exploited as an MRI-based anti-cancer theragnostic agent for solid tumors. Methods: 35 immunocompetent C57BL/6 mice were inoculated with KPC961 pancreatic adenocarcinoma cells in their flank. The 27 mice with the largest tumors at 4 weeks were randomized into 5 cohorts based on treatment: 300 µg of MENP (300; n=6), 600 µg of MENP (600; n=6), 300 µg of low-ME coefficient MENP (LM; n=5), 300 µg of MENP without M1 MRI (NM; MRI field control, n=5), and normal saline (NS; MENP causal effect control; n=5). The 300, 600, LM, and NS cohorts had T2 MRI maps (M0) on a 7T MRI. NM had T2 weighted MRIs at M0. All mice had a neodymium magnet placed over their tumors for 12 hours after tail vein injections (300 µl for all mice) for targeting. The 300, 600, LM, and NS cohorts then underwent MRI mapping (M1) after magnet removal (No M1 MRI for NM). MRI mapping was repeated 5 days after (M2). NM had a T2 weighted MRIs at M2. M1 and M2 data were used to assess relaxation time (contrast effect) and tumor volume from M0, respectively. Student t and ANOVA tests were used to compare differences for tumor volume and relaxation time data and one-sided Fisher’s exact test was used for complete response (CR) data. Results: The median M0 tumor volume was 109.6 mm3 for all mice, and there were no differences between any cohort ( p = 0.978; Table). The 300 and 600 MENP cohorts demonstrated a 102.7% reduction in volume (M2/M0; 56.7% vs. 159.4% for NS and NM controls, p = &lt;0.001) and a 7.2% T2 negative contrast effect (M1/M0; 94.2% vs. 101.3% for NS, p = 0.046) compared to controls. Six mice in 300, 600, and LM (2 each) achieved a clinical CR (between 1 to 2 weeks after M1) vs. none in the NS and NM control cohorts ( p = 0.0418), without any recurrences until end of study (6 weeks after M2). Conclusions: This is the first report demonstrating the theragnostic effects of MENPs having both T2 contrast and locally ablative therapy properties as an in vivo tumor targeting agent. These results confirm prior pilot study and point towards irreversible electroporation as the likely mechanism of action (MOA) since the antitumor effect is not seen within the NM cohort. Additional studies characterizing the MOA, dose-response relationships, and immunomodulatory effects are needed to better understand their full clinical potential.[Table: see text]

The smooth-walled human RVOT contains trabeculations that cause conduction delay

Abstract Funding Acknowledgements None. Background The right ventricular outflow tract (RVOT) is the outlet from the right ventricle and is the initiating substrate of life-threatening arrhythmias. While the luminal wall of the RVOT is often assumed to be without the complex trabecular meshwork that characterizes the right ventricular free wall, the anatomy of the RVOT is an understudied subject. Aim to investigate whether trabeculations occur in the RVOT and to assess whether this impacts electrical propagation. Methods Human hearts were investigated using high-resolution MRI, histology, RNA-sequencing, and optical and electrical mapping. Results We used high-resolution MRI and serial sectioning to reconstruct the macroscopic details of the human RVOT and identified cases exhibiting much trabeculation. The smooth lumen of the RVOT varied between 9% and 23% of the total RV anterior surface (N=11). Histological analysis on additional six hearts indicated that the RVOT compact layer is thinner when trabeculations are present. RNA sequencing of four human donor hearts revealed enrichment in the subendocardial region of 88 genes associated with cardiac conduction and trabeculations (P adjusted&amp;lt;0.05). Finally, we selected two human donor hearts showing trabeculations in the RVOT from which we generated wedge preparation and performed optical and electrical mapping. The trabecular regions demonstrated high degree of fractionation when compared to non-trabeculated regions, which coincided with delayed activation. Conclusion Trabeculations are found in the RVOT, and their extent varies among individuals. This impacts on the thickness of the compact wall in the RVOT, restricting the depth of tissue at which clinical interventions can be performed, as well as influencing electrical propagation and possible arrhythmogenicity.

BRUGADA SYNDROME: NEWEST DATA ON RISK STRATIFICATION

Abstract Background Brugada Syndrome (BrS) is a rare genetically based channelopathy responsible for malignant arrhythmias and sudden cardiac death (SCD) in young adults. Objectives The aims was to evaluate prognostic indicators useful for accurate arrhythmic risk stratification in BrS by studying genetic, clinical, anamnestic, instrumental parameters, and those derived from electrophysiological study (EPS) and intracavitary mapping. Materials and Methods 209 patients with Brugada type 1 were recruited between 01/01/2018 and 01/10/2023. Results In the first study, predictive factors related to high arrhythmic risk from the data obtained for the total population of 209 Brugada patients enrolled in our case series include a positive history of cardiogenic syncope (p value 0.000041), having had a resuscitated cardiac arrest (p value 0.00025), presenting positive EPS for inducibility of ventricular tachycardia (p value 0.00032), having a family history of sudden cardiac death (p value &amp;lt; 0.00001), and presenting positive cardiac mapping and MRI for pathological alterations (both with p value &amp;gt; 0.00001). From the data obtained for the subset of 80 Brugada patients with ICD in our case series, predictive factors related to high arrhythmic risk are different from the previously analyzed population: presenting spontaneous type 1 ECG (p value 0.0015), having had a resuscitated cardiac arrest (p value 0.014028), having a family history of sudden cardiac death (p value &amp;lt; 0.00001), and presenting positive mapping, genetics, and cardiac MRI for pathological alterations. Positive EPS and syncope in this subset do not appear to be risk factors, unlike the population of all 209 enrolled patients. Conclusions Multiparametric scores, including the mentioned markers, have been introduced in clinical practice for a better approach in selection. However, new markers are needed to improve risk stratification in BrS patients, especially those in the so–called "gray zone" with intermediate risk. In the future, it will be evaluated through experimental models and genotype–phenotype integration whether such electrical heterogeneity is also associated with specific genetic or structural abnormalities and may represent a new therapeutic target for etiological treatment in BrS patients. In conclusion, there is an urgent need to develop new methods for risk stratification in Brugada syndrome that are sufficiently sensitive, specific, reproducible, and easy to apply.

Assessment of feto-placental oxygenation and perfusion in a rat model of placental insufficiency using T2* mapping and 3D dynamic contrast-enhanced MRI

IntroductionPlacental insufficiency may lead to preeclampsia and fetal growth restriction. There is no cure for placental insufficiency, emphasizing the need for monitoring fetal and placenta health. Current monitoring methods are limited, underscoring the necessity for imaging techniques to evaluate fetal-placental perfusion and oxygenation. This study aims to use MRI to evaluate placental oxygenation and perfusion in the reduced uterine perfusion pressure (RUPP) model of placental insufficiency. MethodsPregnant rats were randomized to RUPP (n = 11) or sham surgery (n = 8) on gestational day 14. On gestational day 19, rats imaged using a 7T MRI scanner to assess oxygenation and perfusion using T2* mapping and 3D-DCE MRI sequences, respectively. The effect of the RUPP on the feto-placental units were analyzed from the MRI images. ResultsRUPP surgery led to reduced oxygenation in the labyrinth (24.7 ± 1.8 ms vs. 28.0 ± 2.1 ms, P = 0.002) and junctional zone (7.0 ± 0.9 ms vs. 8.1 ± 1.1 ms, P = 0.04) of the placenta, as indicated by decreased T2* values. However, here were no significant differences in fetal organ oxygenation or placental perfusion between RUPP and sham animals. DiscussionThe reduced placental oxygenation without a corresponding decrease in perfusion suggests an adaptive response to placental ischemia. While acute reduction in placental perfusion may cause placental hypoxia, persistence of this condition could indicate chronic placental insufficiency after ischemic reperfusion injury. Thus, placental oxygenation may be a more reliable biomarker for assessing fetal condition than perfusion in hypertensive disorders of pregnancies including preeclampsia and FGR.