Standard MRI Research Articles

Whole-Heart Assessment of Turbulent Kinetic Energy in the Repaired Tetralogy of Fallot

Approximately 10% of congenital heart diseases (CHDs) include Tetralogy of Fallot (TOF). Fortunately, due to advanced surgical techniques, most patients survive until adulthood. However, these patients require frequent monitoring for postoperative complications leading to heart hemodynamic alterations. Turbulent kinetic energy (TKE), as derived from 4D-flow magnetic resonance imaging (4D-flow MRI), has been used to characterize abnormal heart hemodynamics in CHD. Hence, this study aimed to assess the difference in TKE between patients with repaired TOF (rTOF) and healthy volunteers. A total of 35 subjects, 17 rTOF patients and 18 controls, underwent standard-of-care cardiac MRI and research 4D-flow MRI using a clinical 3T scanner. Heart chambers and great vessels were segmented using 3D angiograms derived from 4D-flow MRI. The TKE was quantified within segmented volumes. TKE was compared to standard cardiac MRI metrics. Controls demonstrated higher TKE in the left atria and left ventricle. However, patients demonstrated higher TKE in the right atria, right ventricle (p < 0.05), and pulmonary artery. Lastly, no correlation was observed between TKE and standard clinical measurements. TKE can be a key indicator of the abnormal hemodynamics present in patients with rTOF and can assist future interventions and help monitor long-term outcomes.

Application of a Deep Learning Approach to Analyze Large-Scale MRI Data of the Spine

With its standardized MRI datasets of the entire spine, the German National Cohort (GNC) has the potential to deliver standardized biometric reference values for intervertebral discs (VD), vertebral bodies (VB) and spinal canal (SC). To handle such large-scale big data, artificial intelligence (AI) tools are needed. In this manuscript, we will present an AI software tool to analyze spine MRI and generate normative standard values. 330 representative GNC MRI datasets were randomly selected in equal distribution regarding parameters of age, sex and height. By using a 3D U-Net, an AI algorithm was trained, validated and tested. Finally, the machine learning algorithm explored the full dataset (n = 10,215). VB, VD and SC were successfully segmented and analyzed by using an AI-based algorithm. A software tool was developed to analyze spine-MRI and provide age, sex, and height-matched comparative biometric data. Using an AI algorithm, the reliable segmentation of MRI datasets of the entire spine from the GNC was possible and achieved an excellent agreement with manually segmented datasets. With the analysis of the total GNC MRI dataset with almost 30,000 subjects, it will be possible to generate real normative standard values in the future.

ReIGNITE RT Boost: An International Study Testing the Feasibility, Accuracy and Reliability of Using Restriction Spectrum Imaging (RSI) MRI to Guide Radiotherapy Target Volume Delineation for Prostate Cancer Tumor Boost

<h3>Purpose/Objective(s)</h3> Recently the FLAME clinical trial showed adding a radiation boost to the visible tumor improves prostate cancer control without additional toxicity. In FLAME, a radiologist assisted in each tumor delineation. Even for radiologists, there is substantial dependence on reader experience for prostate MRI. Radiation oncologists' ability to reliably identify prostate tumors is critical to wide adoption and patients benefitting from tumor radiotherapy boost. We have developed a quantitative diffusion MRI metric for prostate cancer based on the restriction spectrum imaging (RSI) framework, called the RSI restriction score (RSI_rs). RSI_rs has been shown to improve accuracy over guideline-recommended standard ADC maps. RSI_rs maps can be overlaid on conventional T2-weighted MRI sequences and used to identify prostate cancer. We hypothesize that contouring on RSI_rs maps will improve the accuracy and reliability of prostate tumor delineation. <h3>Materials/Methods</h3> Radiation oncologists (participants) from multiple institutions contoured prostate tumors on 20 patient cases. An expert radiologist contoured each tumor to establish ground truth. Participants were either board certified or a resident who had completed a clinical genitourinary cancer rotation. Participants were provided the patient's age, PSA level, biopsy result and radiologist's report (e.g., "PI-RADS 5 lesion in right lateral peripheral zone at the base"). Participants delineated volumes on either standard MRI alone (50% of cases; included T2-weighted, DWI, ADC) or standard MRI with RSI_rs map. Accuracy was quantified by comparing to the expert volume by distance to agreement, Dice coefficient, and Jaccard coefficient. Reliability was measured as variation across participants by the Volume Ratio (VR) method. <h3>Results</h3> In this interim analysis of an ongoing study, 126 target volumes have been analyzed from 6 participants. Comparing participant and expert volumes, use of RSI_rs maps significantly improved the mean distance to agreement (3.87mm vs. 1.68mm, p<0.01), Dice coefficient (0.45 vs. 0.65, p<0.001), and Jaccard coefficient (0.32 vs. 0.50, p<0.001). Target volume variability was also significantly improved; VR was reduced from 19.23 to 5.90 (p<0.05). Notably, there were 9 complete misses when participants contoured on standard MRI alone but no misses when RSI_rs maps were provided. 63 global participants have been enrolled in this study and additional data collection and analysis are in process. <h3>Conclusion</h3> The addition of RSI_rs maps to standard MRI improves the reliability and accuracy of target delineation for prostate tumor boost. RSI_rs maps have the potential to increase the feasibility of widely implementing the benefits of focal tumor boost for patients undergoing prostate radiotherapy.

Assessing Radiology Practice Patterns for Obtaining MRI in Pediatric Patients with MR-Conditional Tracheostomy Tubes.

Silicone tracheostomy tubes are a popular choice for pediatric patients with chronic tracheostomies due to their pliability and increased comfort. However, the presence of wire reinforcement causes them to be labeled "MR-conditional." The objective of this study was to understand practice patterns across radiology departments for obtaining MRI in children with MR-conditional tracheostomy tubes. A survey consisting of 7 questions aimed at determining a facility's protocol for obtaining MRI in children with tracheostomy tubes was developed and administered via telephone to MRI technologists at US children's hospitals. 182 children's hospitals were identified and 59 responses were obtained across 30 states (32.4%). 19 sites (32%) were excluded as they were unable to perform MRI. All 40 facilities reported that they have a standard questionnaire for medical implants, however only 20 reported that tracheostomy tubes are included on that questionnaire (50%). 6 (15%) reported all MR-conditional tubes are changed to MR-safe ones. Of the remaining 34, protocols were as follows: 1 (2.9%) scans patients with conditional tubes for a maximum of 15 minutes, 5 (14.7%) only use a 1.5T magnet, and 28 (82.3%) reported following the manufacturer conditions. In terms of artifact, 3 sites change MR-conditional tubes to MR-safe if scanning the head, neck, chest, or abdomen (8.8%), 6 (17.6%) change the tube if scanning the head or neck, 15 (44.1%) change the tube only if scanning the neck, and 10 (29.4%) were not aware of issues with artifact. Based on this survey of MRI technologists at US children's hospitals, there is no unified protocol for obtaining MRI in pediatric patients with MR-conditional tracheostomy tubes. A lack of standardized protocols may be contributing to unnecessary tracheostomy changes. Future research includes clearly defining the anatomical regions affected by wire-related artifact and developing a standardized MRI protocol for these patients.

Development of Real-Time Kinematic Magnetic Resonance Imaging (kMRI) Techniques for Studying the Kinematics of the Spine and Joints in Dogs-Preliminary Study on Cadavers.

Simple SummaryMany orthopedic and neurological pathologic conditions can potentially lead to or be affected by joint instability. Standard magnetic resonance imaging, as a static technique that examine joints and body parts in functional rest, can underestimate or overlook key diagnostic findings. As a result, kinematic magnetic resonance imaging techniques were developed to evaluate joints and body parts under stress and load conditions or during movement. In human medicine, the real-time acquisition technique is one of the modalities for acquiring kinematic magnetic resonance imaging, and has gained popularity in recent years. This proof-of-concept study was designed to test the feasibility of real-time acquisition techniques in veterinary medicine for the first time. Based on the results of this preliminary cadaveric study, real-time kinematic magnetic resonance imaging may be a feasible and valuable procedure to be applied to the canine cervical spine and stifle joints. Moreover, given the ease of execution and the concise duration of acquisitions, it could be applied in a regular standard protocol MRI with little additional effort, risk, and cost. In this proof-of-concept study, a good visualization of the canine cervical spine and stifle joint was achieved, showing the potential of real-time acquisition techniques for clinical and research applications.Kinematic MRI (kMRI) is a novel human imaging technique that couples the excellent soft tissue contrast and multiplanar capabilities of traditional MRI with kinematic potential. The study’s goals are: (1) testing the feasibility of spinal cord and joints real-time kMRI; and (2) evaluating the quality of these kinematic studies as a new diagnostic option in veterinary medicine. Standard and real-time kinematic MRI were performed on cervical spine, elbow, and stifle joints of seven cadavers. Studies were repeated after a surgical insult aimed to create a certain degree of joint instability. A total of 56 MRI were performed—7 cervical spinal tracts, 3 elbow joints, and 4 stifle joints were examined. The technique was feasible in all the three regions examined. The images were considered of excellent quality for the stifle joint, good to fair for the cervical spine, whereas two of three elbow studies were considered to have unacceptable image quality. Additionally, real-time kMRI provided good to excellent information about stifle instability. Therefore we consider kMRI a promising technique in veterinary medicine. Further studies and an in vivo setting are needed to increase the quality of the kMRI images, and to fully evaluate clinical usefulness.

Clinical Value of Diffusion-Weighted Whole-Body Imaging with Background Body Signal Suppression (DWIBS) for Staging of Patients with Suspected Head and Neck Cancer.

(1) Background: To determine the importance of diffusion-weighted whole-body MRI with background body signal suppression (DWIBS) in the staging process of patients with suspected head and neck carcinomas. (2) Methods: A total of 30 patients (24 male, 6 female) with a median age of 67 years with clinically suspected head and neck carcinoma with pathologic cervical nodal swelling in ultrasound underwent the staging procedure with computed tomography (CT) and whole-body MRI including DWIBS. (3) Results: In a total of 9 patients, abnormalities in the routine work-up of pretherapeutic staging were found. Five cases of either secondary cancer or distant metastases were only visible in DWIBS, while being missed on CT. One diagnosis was only detectable in CT and not in DWIBS, whereas three diagnoses were recognizable in both modalities. (4) Conclusions: DWIBS in addition to a standard neck MRI in cervical lymphadenopathy suspicious for head and neck cancer yielded additional clinically relevant diagnoses in 17% of cases that would have been missed by current staging routine procedures. DWIBS offered a negative predictive value of 98.78% for ruling out distant metastases or secondary malignancies.

Gastroenteropancreatic neuroendocrine neoplasm imaging: standard reporting templates.

Standardized reporting in radiology has an established role in numerous disease processes, with added benefits in oncology of reduced variability, and generation of a thorough and pertinent report with a focused and relevant conclusion. Many radiologists are not familiar with the imaging patterns of neuroendocrine neoplasm (NEN) spread and recurrence. This paper will present standardized CT, MRI, and PET templates for reporting gastroenteropancreatic (GEP) NENs and explain the rationale for including specific pertinent positive and negative findings, at various stages of disease management, based on site of origin. Basic templates for initial and follow-up anatomic and molecular GEP NEN imaging were created with input from the multidisciplinary Society of Abdominal Radiology (SAR) Neuroendocrine Tumor Disease Focused Panel (NET-DFP). The templates were further modified and finalized after several iterations. Four main report templates were generated for (i) initial anatomic CT or MR imaging studies, (ii) follow-up anatomic CT or MR imaging studies, (iii) initial Somatostatin Receptor (SSTR) or FDG PET imaging studies, and (iv) follow-up SSTR or FDG PET imaging studies. Each study template was formatted to allow its integration into a dictation software directly and be modified as needed, with internalized instructions indicating where a drop-down menu or macro may be used to personalize the template as necessary. These templates were created through a combination of multidisciplinary expert opinion discussion supported by literature review and provide basic structured reporting standards for GEP NEN anatomic and molecular imaging studies.

Predictors of infraspinatus muscle degeneration in individuals with an isolated supraspinatus tendon tear.

Determine the demographic and clinical factors that predict infraspinatus muscle degeneration in individuals with an isolated supraspinatus tendon tear. A retrospective analysis was performed using the medical records of patients who had a shoulder MRI interpreted by 1 of 3 fellowship-trained musculoskeletal radiologists since the implementation of a standardized MRI 3T protocol within our healthcare system. Demographic (e.g., age, sex) and clinical data (e.g., tear size, muscle degeneration, co-morbidities) were collected. Patients with an isolated supraspinatus tendon tear (n = 121) were assigned to one of two groups based on whether any infraspinatus muscle degeneration was present. Logistic regression was used to assess the univariate relationships between infraspinatus muscle degeneration and patient and clinical data, while least absolute shrinkage and selector operator (LASSO) logistic regression was used to assess the multivariable relationship. Of the patients with an isolated supraspinatus tendon tear, 16.5% had evidence of infraspinatus muscle degeneration. The presence of infraspinatus muscle degeneration was independently associated with cardiovascular disease (P = 0.01), supraspinatus muscle degeneration (P < 0.01), and subscapularis muscle degeneration (P = 0.01). When the multivariable relationship is assessed, supraspinatus muscle degeneration emerged as the only variable of significant importance for detecting infraspinatus muscle degeneration (specificity: 87.1%, sensitivity: 80.0%). Infraspinatus muscle degeneration is not uncommon in individuals with an isolated supraspinatus tear and is most associated with concomitant supraspinatus muscle degeneration. These findings highlight the need for clinicians to specifically assess the status of each rotator cuff muscle, even when the tendon itself is intact.

Impaired myocardial calcium handling in people with type 2 diabetes: an in vivo manganese-enhanced magnetic resonance imaging study

Abstract Background There is a high prevalence of subclinical cardiac dysfunction in people with type 2 diabetes (T2D) which is associated with subsequent development of heart failure. Dysregulated myocardial calcium handling has been demonstrated in animal models of T2D and may be a key mechanism driving the development of heart failure. Manganese-enhanced cardiac magnetic resonance imaging (MEMRI) provides a unique method to assess in vivo myocardial calcium handling. Purpose To determine whether myocardial calcium handling is perturbed in people with T2D with no history of cardiovascular disease. We hypothesised that myocardial manganese uptake would be reduced in people with T2D compared with healthy volunteers. Methods Cross-sectional case-control study, adults with (n=20) and without (n=9) T2D underwent both gadolinium-enhanced MRI and MEMRI. Standard gadolinium-enhanced MRI was used to assess cardiac structure, function and tissue characteristics. MEMRI scans were performed within two weeks of the initial scan. Native T1 maps were obtained in the mid-short axis slice position using a Modified Look-Locker Inversion recovery sequence. An intravenous infusion of manganese dipyridoxyl diphosphate (5 μmol/kg (0.1 mL/kg) at 1 mL/min) was administered and T1 maps at the same location were repetitively acquired every 2.5 min for 30 min. Regions of interest were drawn in the inferoseptal segment and blood pool for all T1 maps from 0 to 30 min by a single observer. The primary outcome was the rate of manganese uptake which was assessed by Patlak modelling as a measure of myocardial calcium handling. Manganese uptake constants were compared using analysis of co-variance, with age, sex and body mass index as co-variates. Results Subjects with T2D were older (62±7 vs. 57±5 years, p=0.046) but body mass index (29.0±4.5 vs. 26.2±3.4 kg/m2, p=0.106), systolic (135±16 vs. 134±17 mmHg, p=0.809) and diastolic (81±10 vs. 83±9 mmHg, p=0.736) blood pressures were similar. Compared to control subjects, participants with T2D had normal systolic function but more concentric left ventricular remodelling (mass/volume ratio 0.90±0.14 vs. 0.71±0.06 g/mL, p&amp;lt;0.001) and reduced peak early diastolic strain rate (0.64±0.17 vs. 0.91±0.26 s–1, p=0.002). Myocardial manganese uptake was substantially reduced in people with T2D compared with controls (6.51±1.46 vs. 8.45±2.52 ml/100 g of tissue/min, p=0.003) (Figure 1). Conclusions For the first time, we have demonstrated in vivo that despite no history of cardiovascular disease and normal systolic function, patients with T2D have marked impairment of myocardial calcium handling. This has potential major implications for the pathogenesis, diagnosis and treatment of diabetic cardiomyopathy. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation and National Institute for Health Research

Multi-atlas thalamic nuclei segmentation on standard T1-weighed MRI with application to normal aging.

Specific thalamic nuclei are implicated in healthy aging and age-related neurodegenerative diseases. However, few methods are available for robust automated segmentation of thalamic nuclei. The threefold aims of this study were to validate the use of a modified thalamic nuclei segmentation method on standard T1 MRI data, to apply this method to quantify age-related volume declines, and to test functional meaningfulness by predicting performance on motor testing. A modified version of THalamus Optimized Multi-Atlas Segmentation (THOMAS) generated 22 unilateral thalamic nuclei. For validation, we compared nuclear volumes obtained from THOMAS parcellation of white-matter-nulled (WMn) MRI data to T1 MRI data in 45 participants. To examine the effects of age/sex on thalamic nuclear volumes, T1 MRI available from a second data set of 121 men and 117 women, ages 20-86 years, were segmented using THOMAS. To test for functional ramifications, composite regions and constituent nuclei were correlated with Grooved Pegboard test scores. THOMAS on standard T1 data showed significant quantitative agreement with THOMAS from WMn data, especially for larger nuclei. Sex differences revealing larger volumes in men than women were accounted for by adjustment with supratentorial intracranial volume (sICV). Significant sICV-adjusted correlations between age and thalamic nuclear volumes were detected in 20 of the 22 unilateral nuclei and whole thalamus. Composite Posterior and Ventral regions and Ventral Anterior/Pulvinar nuclei correlated selectively with higher scores from the eye-hand coordination task. These results support the use of THOMAS for standard T1-weighted data as adequately robust for thalamic nuclear parcellation.

Serum Sirtuin-1, HMGB1-TLR4, NF-KB and IL-6 Levels in Alzheimer's: The Relation Between Neuroinflammatory Pathway and Severity of Dementia.

In this study, serum Sirtuin-1(SIRT-1), High Mobility Group Box 1 (HMGB1), Toll-Like Receptor-4 (TLR4), Nuclear Factor Kappa B (NF-kB), Interleukin-6 (IL-6), Amyloid βeta-42 (Aβ- 42), and p-tau181 levels in patients diagnosed with AD according to NINCS-ADRA criteria were studied. We investigated the inflammatory pathways that lead to progressive neuronal loss and highlight their possible relationship with dementia severity in the systemic circulation. Patients over 60 years of age were grouped according to their Standard Mini Mental Test results, MRI, and/or Fludeoxyglucose positron emission tomography or according to their CT findings as Control n:20; AD n:32; Vascular Dementia (VD) n:17; AD + VD; n = 21. Complete blood count, Glucose, Vitamin B12, Folic Acid, Enzymes, Urea, Creatinine, Electrolytes, Bilirubin, and Thyroid Function tests were evaluated. ELISA was used for the analysis of serum SIRT1, HMGB1, TLR4, NF-kB, IL-6, Aβ-42, and p-tau181 levels. Levels of serum Aβ-42, SIRT1, HMGB1, and IL-6 were significantly higher (p< 0.001, p< 0.01, p< 0.001, and p< 0.001, respectively), and TLR4 levels were significantly lower (p< 0.001) in the dementia group than in the control group. No significant difference was observed between dementia and control groups for serum NF-kB and p-tau181 levels. Our results show that the levels of the Aβ42, SIRT 1, HMGB1, and TLR4 pathways are altered in AD and VD. SIRT 1 activity plays an important role in the inflammatory pathway of dementia development, particularly in AD.

Diagnostic Evolution of Synchronous Arteriovenous Malformation &amp; Glioblastoma: A Case Report

Abstract AIMS We present the clinical course, radiology and histopathology of a case with synchronous pathology and aim to highlight learning points and diagnostic pitfalls. METHOD Case Notes, Radiology and Pathology were reviewed. RESULTS A 25 year old female with learning difficulties presented acutely with collapse. Initial CT-imaging demonstrated a right peritrigonal parenchymal haematoma with intraventricular extension. CT-Angiography revealed small vessels around the haematoma but no definite underlying vascular abnormality. Whilst the standard MRI sequences appeared to confirm the CT findings, the patient was unable to tolerate the planned MR angiogram or post-contrast sequences. Three months later, Digital Subtraction Angiography (DSA) revealed an “unusual” arteriovenous malformation (AVM) at the site of the previous haematoma. Over the following two months, the patient represented twice with acute headaches. CT imaging each time demonstrated further re-bleeds, with increasing oedema. Consequently, another DSA was performed for attempted embolisation but striking differences in the appearance of the AVM were now evident. Stereotactic radiosurgery was scheduled, but a planning CT-scan six weeks later revealed, for the first time, appearances suggestive of an underlying high-grade neoplasm. A biopsy was performed which showed a Glioblastoma (CNS WHO, 2021; Grade 4) alongside an arteriovenous malformation with well-developed arterial and venous structures. Despite optimal ICU management post-operatively, the patient deteriorated and sustained irreversible brain damage from which she did not recover. CONCLUSION Synchronous Glioblastoma and AVM is rare and can cause diagnostic and surgical challenges. These difficulties and the proposed angiogenic effects of tumour factors, as underlying aetiological agents of these synchronous lesions, is discussed.

‘Haleem's Hen’: A Mnemonic for the Anatomy of Hindfoot Structures at the Level of Sustentaculum Tali on Coronal T1-Weighted Magnetic Resonance Images

Category: Hindfoot; Ankle Introduction/Purpose: Magnetic resonance anatomy of the hindfoot as seen at the level of the sustentaculum tali is intricate due to surrounding muscles, tendons, aponeurosis and ligaments. The objective of this work is to provide a mnemonic with illustrative figures to simplify this complex anatomical region on coronal T1-weighted magnetic resonance images (T1-MRIs). Methods: One hundred and twenty-four patients referred for foot and ankle complaints were scanned utilizing standard MRI imaging protocols for evaluation of the hindfoot. Only coronal T1-MRIs of the calcaneus at the level of sustentaculum tali of unremarkably reported patients were selected for the development of this mnemonic. T1- and T2-MRIs of an additional set of patients with hindfoot pathologies were selected to demonstrate how this mnemonic is adapted to identify specific pathologies. Results: Upon viewing the calcaneus with the adjacent anatomical structures on coronal T1-MRIs, the overall appearance resembles a ''Hen in the Nest with Four Eggs.'' The calcaneus represents the body of the hen, while the sustentaculum tali forms the head and neck. The posterior tibial tendon represents the crest of the hen, and the flexor digitorum longus and flexor hallucis longus tendons represent its beak and wattle, respectively. The peroneus brevis and peroneus longus tendons represent the tail, and the long plantar ligament represents the flexed legs of Haleem's hen. The plantar aponeurosis represents the hen's nest. Whereas the abductor hallucis, flexor digitorum brevis, abductor digiti minimi and quadratus plantae muscles are the four eggs. Pes planus, flexor digitorum brevis hemangioma, Baxter's neuropathy associated with chronic denervation abductor digiti minimi atrophy and peroneal tendonitis are some of the hindfoot pathologies that can be identified utilizing the mnemonic. Conclusion: The mnemonic, 'Haleem's Hen in the Nest with Four Eggs,' serves as a simplified phrase for orthopedic surgeons, radiologists and other physicians to easily recall the anatomy of the hindfoot when viewing it at the level of the sustentaculum tali on coronal T1-MRIs. In addition, this mnemonic could be particularly useful when utilized in medical education curriculum for residents, fellows, and medical students. Further research is required to validate this mnemonic as an educational tool in medical training and detail additional hindfoot pathologies that can be identified with it.

Standardization of MRI Screening and Reporting in Individuals With Elevated Risk of Pancreatic Ductal Adenocarcinoma: Consensus Statement of the PRECEDE Consortium.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with a dismal survival rate. Screening the general population for early detection of PDAC is not recommended, but because early detection improves survival, high-risk individuals, defined as those meeting criteria based on a family history of PDAC and/or the presence of known pathogenic germline variant genes with PDAC risk, are recommended to undergo screening with MRI and/or endoscopic ultrasound at regular intervals. The Pancreatic Cancer Early Detection (PRECEDE) Consortium was formed in 2018 and is composed of gastroenterologists, geneticists, pancreatic surgeons, radiologists, statisticians, and researchers from 40 sites in North America, Europe, and Asia. The overarching goal of the PRECEDE Consortium is to facilitate earlier diagnosis of PDAC for high-risk individuals to increase survival of the disease. A standardized MRI protocol and reporting template are needed to enhance the quality of screening examinations, improve consistency of clinical management, and facilitate multiinstitutional research. We present a consensus statement to standardize MRI screening and reporting for individuals with elevated risk of pancreatic cancer.

Acceleration of neuromelanin-sensitive MRI sequences in the substantia nigra using standard MRI options

PurposeNeuromelanin MRI (NM-MRI) is applied as a proxy measurement of dopaminergic functioning of the substantia nigra pars compacta (SN). To increase its clinical applicability, a fast and easily applicable NM-MRI sequence is needed. This study therefore compared accelerated NM-MRI sequences using standard available MRI options with a validated 2D gradient recalled echo NM-MRI sequence with off-resonance magnetization transfer (MT) pulse (2D-MToffRes).MethodsWe used different combinations of compressed sense (CS) acceleration, repetition times (TR), and MT pulse to accelerate the validated 2D-MToffRes. In addition, we compared a recently introduced 3D sequence with the 2D-MToffRes.ResultsOur results show that the 2D sequences perform best with good to excellent reliability. Only excellent intraclass correlation coefficients were found for the CS factor 2 sequences.ConclusionWe conclude that there are several reliable approaches to accelerate NM-MRI, in particular by using CS.

A novel serum extracellular vesicle protein signature to monitor glioblastoma tumor progression.

Detection of tumor progression in patients with glioblastoma remains a major challenge. Extracellular vesicles (EVs) are potential biomarkers and can be detected in the blood of patients with glioblastoma. In our study, we evaluated the potential of serum-derived EVs from glioblastoma patients to serve as biomarker for tumor progression. EVs from serum of glioblastoma patients and healthy volunteers were separated by size exclusion chromatography and ultracentrifugation. EV markers were defined by using a proximity-extension assay and bead-based flow cytometry. Tumor progression was defined according to modified RANO criteria. EVs from the serum of glioblastoma patients (n=67) showed an upregulation of CD29, CD44, CD81, CD146, C1QA and histone H3 as compared to serum EVs from healthy volunteers (P value range: <.0001 to .08). For two independent cohorts of glioblastoma patients, we noted upregulation of C1QA, CD44 and histone H3 upon tumor progression, but not in patients with stable disease. In a multivariable logistic regression analysis, a combination of CD29, CD44, CD81, C1QA and histone H3 correlated with RANO-defined tumor progression with an AUC of 0.76. Measurement of CD29, CD44, CD81, C1QA and histone H3 in serum-derived EVs of glioblastoma patients, along with standard MRI assessment, has the potential to improve detection of true tumor progression and thus could be a useful biomarker for clinical decision making.

Advanced MRI imaging of nerve roots in lumbar radiculopathy due to discoradicular conflict: DWI, DTI, and T2 mapping with clinical and neurophysiological correlations.

To evaluate the lumbar nerve root alterations in patients with lumbar disc herniation sciatica using advanced multimodality MRI sequences and the correlations with clinical and neurophysiological findings. We prospectively evaluated 45 patients suffering from unilateral lumbar radiculopathy due to disco radicular conflict. All patients underwent MRI examinations using a standard MRI protocol and additional advanced MRI sequences (DWI, DTI, and T2 mapping sequences). Relative metrics of ADC, FA, and T2 relaxation times were recorded by placing ROIs at the pre-, foraminal, and post-foraminal level, either at the affected side or the contralateral side, used as control. All patients were also submitted to electromyography testing, recording the spontaneous activity, voluntary activity, F wave amplitude, latency, and motor evoked potentials (MEP) amplitude and latency, both at the level of the tibialis anterior and the gastrocnemius. Clinical features (diseases duration, pain, sensitivity, strength, osteotendinous reflexes) were also recorded. Among clinical features, we found a positive correlation of pain intensity with ADC values of the lumbar nerve roots. The presence of spontaneous activity was correlated with lower ADC values of the affected lumbar nerve root. F wave and MEP latency were correlated with decreased FA values at the foraminal level and increased values at the post-foraminal level. The same neurophysiological measures correlated positively with pre-foraminal T2 mapping values and negatively with post-foraminal T2 mapping values. Increased T2 mapping values at the foraminal level were correlated with disease duration. Evaluation of lumbar nerve roots using advanced MRI sequences may provide useful clinical information in patients with lumbar radiculopathy, potentially indicating active inflammation/myelinic damage (DTI, T2 mapping) and axonal damage/chronicity (DWI).

Meningioma in patients exposed to progestin drugs: results from a real-life screening program.

To report the results of systematic meningioma screening program implemented by French authorities in patients exposed to progestin therapies (cyproterone (CPA), nomegestrol (NA), and chlormadinone (CMA) acetate). We conducted a prospective monocentric study on patients who, between September 2018 and April 2021, underwent standardized MRI (injection of gadolinium, then a T2 axial FLAIR and a 3D-T1 gradient-echo sequence) for meningioma screening. Of the 210 included patients, 15 (7.1%) had at least one meningioma; seven (7/15, 47%) had multiple meningiomas. Meningiomas were more frequent in older patients and after exposure to CPA (13/103, 13%) compared to NA (1/22, 4%) or CMA (1/85, 1%;P = 0.005). After CPA exposure, meningiomas were associated with longer treatment duration (median = 20 vs 7years,P = 0.001) and higher cumulative dose (median = 91g vs. 62g,P = 0.014). Similarly, their multiplicity was associated with higher dose of CPA (median = 244g vs 61g,P = 0.027). Most meningiomas were ≤ 1 cm3 (44/58, 76%) and were convexity meningiomas (36/58, 62%). At diagnosis, patients were non-symptomatic, and all were managed conservatively. Among 14 patients with meningioma who stopped progestin exposure, meningioma burden decreased in 11 (79%) cases with no case of progression during MR follow-up. Systematic MR screening in progestin-exposed patients uncovers small and multiple meningiomas, which can be managed conservatively, decreasing in size after progestin discontinuation. The high rate of meningiomas after CPA exposure reinforces the need for systematic screening. For NA and CMA, further studies are needed to identify patients most likely to benefit from screening.

P03.11.A Potential role of pre-radiotherapy MRI for target delineation in high-grade gliomas: a multicenter retro-prospective cohort study

Abstract Background The optimal timing for target identification in high-grade glioma (HGG) remains unclear due to variability in the hyper-signal T2/FLAIR between MRI performed at diagnosis, post-surgery and at radiotherapy (RT) start. The aim of this study was to retrospectively confirm that RT planned on delayed MRI might allow to spare more normal tissue without decreasing local tumour control, in order to prospectively evaluate the best standard and advanced MRI and metabolic imaging sequences for clinical tumor volume (CTV) adaptation. Material and Methods We analyzed a retrospective cohort of consecutive patients with HGG treated from 2017 to 2020. All patients had a diagnostic MRI and another performed immediately post-surgery or pre-RT. Target volumes were contoured, based on T2/FLAIR, on diagnostic and post-surgery MRI in group A, while in group B on pre-RT MRI. We analyzed GTV and CTV volume, and the percentage increase between them. Moreover, we compared the two groups in terms of clinical-pathological characteristics and progression-free survival (PFS) and overall survival (OS). A prospective study, started on January 2022, has enrolled patients with HGG evaluated by advanced sequences MRI at diagnosis, post-surgery and pre-RT. In addition, some selected patients have undergone diagnostic DOPA-PET and pre-RT DOPA-PET. 2 MRI-guided contours have been performed for each patient: adapted on T2/FLAIR post-surgery and CTV-adapt on pre-RT, to assess study objectives. Results In retrospective cohort we analyzed 54 patients (25 group A, 29 group B). The median age of patients was 61 years (IQR 17,75), 93% had an ECOG PS of 0 or 1, 51 were symptomatic at diagnosis. Patients in group B had more frequently MGMT methylation (59 % vs. 28%, p=0.01) while less frequently frontal lobe involvement (60% vs. 24%, p=0.01). The median percentage increase between GTV and CTV was higher in group A than B: 431% (range 62%-7335%) vs 385% (range 53%-3174%), respectively. No significant difference in the pattern of relapse was observed, since &amp;gt;90% of disease recurrences were in-field in both groups. Median PFS and OS of the overall population were 9.5 months (95% CI 7 - 12) and 18.5 months (95% CI 16 - 24), respectively. Patients in group B had a significant better PFS as compared to those in group A (p=0.03), but similar OS. Nevertheless, imbalance in MTMT methylation status between the two groups was a major driver for PFS. Overall, 37 out of 51 patients had improvement in neurological symptoms (p&amp;lt;0.001), with no difference between the two groups (p=0.54). Conclusion Our data suggest that CTV adaptation to pre-RT T2/FLAIR may allow reducing RT volume, without affecting symptoms relieving and disease control. Results from the prospective study will help identifying the best adaptation of CTV guided by T2/FLAIR, advanced MRI sequences and metabolic imaging, in order to optimize efficacy and safety of treatment planning.

OS07.4.A Regorafenib in recurrent glioblastoma patients: a multicentric real-life study

Abstract Background Few options are still available for recurrent glioblastoma (GBM). In the Italian phase 2 REGOMA trial, regorafenib improved overall survival, as compared to lomustine, for GBM patients at first progression after chemoradiation. Here, we present the results of a real-life multicentre study that analysed clinical and radiological features, response to treatments, tolerability, and outcome of a cohort of GBM patients treated with regorafenib at first tumour progression. Patients and Methods We enrolled GBM patients at first tumour progression in three Italian Institutions (Turin, Treviso, Bari). Regorafenib was administered following an escalation dose protocol (1st cycle: 80 mg/day for 2 weeks, then 120 mg/day for one week; 2nd cycle: 120 mg/day for 2 weeks, then 160 mg/day for one week; 160 mg/day from the 3rd cycle). MRI scans were obtained at baseline and every 3 months. Progression-free survival (PFS) and overall survival (OS) were defined as time from regorafenib initiation and disease progression or death. Results From January 2020 to January 2022, 66 GBM patients were included. Median age was 60.0 years. MGMTp methylation was found in 30 patients (45.5%). First-line treatment consisted in chemoradiation in 61 (92.4%), in upfront TMZ (3, 4.5%) or RT alone followed by TMZ (2, 3.0%). Median dose was 120 mg/day 21q28 day, which was lower than that used in REGOMA trial (149 mg). Median PFS (mPFS) was 2.7 months (2.4 - 3.0 95% CI) and median OS (mOS) 7.1 months (5.4 - 8.9 95% CI). Best RANO response to regorafenib was partial response (PR) in 10 (15.1%), stable disease in 14 (21.2%), and progressive disease in 42 (63.7%) patients. All PRs were observed within the first three months of treatment. Patients who completed treatment up the 6th, 9th, and 12th cycles were 20, 3 and 2, respectively. Forty-six (69.7%) patients presented adverse events of any grade, and 21 (31.8%) grade III-IV toxicity. The most frequent adverse events were fatigue (33.3%), hand-foot syndrome (27.3%), and liver enzymes increase (15.2%). Two patients only (3.0%) interrupted regorafenib due to toxicity.In a multivariable analysis, factors significantly associated with disease progression were higher age (p = 0.035) and absence of MGMTp methylation (p = 0.024). Conclusion In this real-life study on 66 patients, mPFS and mOS were similar to those of the 59 patients enrolled in the regorafenib arm of REGOMA trial (2.7 vs 2.0 months; 7.1 vs 7.4 months, respectively). However, we observed a higher rate of PRs as compared to REGOMA (15% versus 3.0%). Type and severity of adverse events were similar between the two studies. Moreover, we had a lower incidence of discontinuations of regorafenib due to toxicity, maybe attributable to the lower dose intensity.We are further analysing the data of MRI-perfusion, with the aim to explore whether it can predict an early response or progression in comparison to standard MRI.