Serial Magnetic Resonance Imaging Research Articles

Reduction in Radiologist Interpretation Time of Serial CT and MR Imaging Findings with Deep Learning Identification of Relevant Priors, Series and Finding Locations

Finding comparison to relevant prior studies is a requisite component of the radiology workflow. The purpose of this study was to evaluate the impact of a deep learning tool simplifying this time-consuming task by automatically identifying and displaying the finding in relevant prior studies. The algorithm pipeline used in this retrospective study, TimeLens (TL), is based on natural language processingand descriptor-based image-matching algorithms. The dataset used for testing comprised 3872 series of 246 radiology examinations from 75 patients (189 CTs, 95 MRIs). To ensure a comprehensive testing, five finding types frequently encountered in radiology practice were included: aortic aneurysm, intracranial aneurysm, kidney lesion, meningioma, and pulmonary nodule. After a standardized training session, nine radiologists from three university hospitals performed two reading sessions on a cloud-based evaluation platform resembling a standard RIS/PACS. The task was to measure the diameter of the finding-of-interest on two or more exams (a most recent and at least one prior exam): first without use of TL, and a second session at an interval of at least 21 days with the use of TL. All user actions were logged for each round, including time needed to measure the finding at all timepoints, number of mouse clicks, and mouse distance traveled. The effect of TL was evaluated in total, per finding type, per reader, per experience (resident vs. board-certified radiologist), and per modality. Mouse movement patterns were analyzed with heatmaps. To assess the effect of habituation to the cases, a third round of readings was performed without TL. Across scenarios, TL reduced the average time needed to assess a finding at all timepoints by 40.1% (107 vs. 65seconds; p<0.001). Largest accelerations were demonstrated for assessment of pulmonary nodules (-47.0%; p<0.001). Less mouse clicks (-17.2%) were needed for finding evaluation with TL, and mouse distance traveled was reduced by 38.0%. Time needed to assess the findings increased from round 2 to round 3 (+27.6%; p<0.001). Readers were able to measure a given finding in 94.4% of cases on the series initially proposed by TL as most relevant series for comparison. The heatmaps showed consistently simplified mouse movement patterns with TL. A deep learning tool significantly reduced both the amount of user interactions with the radiology image viewer and the time needed to assess findings of interest on cross-sectional imaging with relevant prior exams.

Effects of anesthesia exposure on postnatal maturation of white matter in rhesus monkeys.

There is increasing concern about the potential effects of anesthesia exposure on the developing brain. The effects of relatively brief anesthesia exposures used repeatedly to acquire serial magnetic resonance imaging scans could be examined prospectively in rhesus macaques. We analyzed magnetic resonance diffusion tensor imaging (DTI) of 32 rhesus macaques (14 females, 18 males) aged 2weeks to 36 months to assess postnatal white matter (WM) maturation. We investigated the longitudinal relationships between each DTI property and anesthesia exposure, taking age, sex, and weight of the monkeys into consideration. Quantification of anesthesia exposure was normalized to account for variation in exposures. Segmented linear regression with two knots provided the best model for quantifying WM DTI properties across brain development as well as the summative effect of anesthesia exposure. The resulting model revealed statistically significant age and anesthesia effects in most WM tracts. Our analysis indicated there were major effects on WM associated with low levels of anesthesia even when repeated as few as three times. Fractional anisotropy values were reduced across several WM tracts in the brain, indicating that anesthesia exposure may delay WM maturation, and highlight the potential clinical concerns with even a few exposures in young children.

Ischemic Cerebellar Stroke in a Young Patient with Neurofibromatosis Type 2, a Case Report (P12-5.026)

<h3>Objective:</h3> We present a case of brainstem ischemia in a young patient with neurofibromatosis 2 (NF2) and review the existing literature on similar cases, which together suggest a possible NF2-associated syndrome of which stroke neurologists and pediatric neurologists should be aware. <h3>Background:</h3> NF2 is a multifaceted disease characterized primarily by benign CNS tumors, especially meningiomas and vestibular schwannomas. There have been several cases of brainstem ischemic stroke in young NF2 patients reported in the literature. To date, there is no unified theory about the connection between NF2 and pediatric stroke. <h3>Design/Methods:</h3> We present a case of ischemia in the left cerebellar peduncle of a young patient with NF2, as well as a narrative review of the literature on previous cases. <h3>Results:</h3> The patient presented to the Emergency Department with left facial paresthesia and dizziness. Serial Magnetic Resonance Images (MRI’s) displayed an initial area of restricted diffusion in the left cerebellar peduncle with peripheral enhancement which did improve over several months, consistent with maturing infarct. <h3>Conclusions:</h3> Our case joins several others with similar presentations and findings, including pediatric patients for whom brainstem ischemia was the presenting symptom of NF2. The primary theory for the cause of brainstem ischemia in juvenile NF2 is a microvascular cause due to genetic deficiency of <i>neurofibromin 2</i>, a regulator of endothelial development, whose absence is likely to disrupt vascular homeostatic mechanisms. Multicenter studies with large NF2 cohorts are needed to better characterize this syndrome. Understanding brainstem ischemia in young NF2 patients will inform the development of treatment guidelines for such patients. <b>Disclosure:</b> An immediate family member of Mrs. Trautman has received personal compensation for serving as an employee of Hydro Extrusions. Mrs. Trautman has received personal compensation for serving as an employee of University of South Dakota. Dr. Sandhu has nothing to disclose.

Persistence of Human Immunodeficiency Virus-Associated Cerebral Toxoplasmosis Lesions in Successfully Treated Patients Receiving Combination Antiretroviral Therapy.

Toxoplasmic encephalitis (TE) is a life-threatening complication of people with human immunodeficiency virus (PWH) with severe immunodeficiency, especially those with a CD4+ T-cell count <100 cells/µL. Following a clinical response to anti-Toxoplasma therapy, and immune reconstitution after initiation of combination antiretroviral therapy (ART), anti-Toxoplasma therapy can be discontinued with a low risk of relapse. To better understand the evolution of magnetic resonance imaging (MRI)-defined TE lesions in PWH receiving ART, we undertook a retrospective study of PWH initially seen at the National Institutes of Health between 2001 and 2012, who had at least 2 serial MRI scans. Lesion size and change over time were calculated and correlated with clinical parameters. Among 24 PWH with TE and serial MRI scans, only 4 had complete clearance of lesions at the last MRI (follow-up, 0.09-5.8 years). Of 10 PWH off all anti-Toxoplasma therapy (median, 3.2 years after TE diagnosis), 6 had persistent MRI enhancement. In contrast, all 5 PWH seen in a pre-ART era study who were followed for >6 months had complete clearance of lesions. TE lesion area at diagnosis was associated with the absolute change in area (P < .0001). Contrast enhancement can persist even when TE has been successfully treated and anti-Toxoplasma therapy has been stopped, highlighting the need to consider diagnostic alternatives in successfully treated patients with immune reconstitution presenting with new neurologic symptoms.

Detection of Atrial Fibrillation Using Insertable Cardiac Monitors in Patients With Cryptogenic Stroke in Japan (the LOOK Study): Protocol for a Prospective Multicenter Observational Study

Paroxysmal atrial fibrillation (AF) is a probable cause of cryptogenic stroke (CS), and its detection and treatment are important for the secondary prevention of stroke. Insertable cardiac monitors (ICMs) are clinically effective in screening for AF and are superior to conventional short-term cardiac monitoring. Japanese guidelines for determining clinical indications for ICMs in CS are stricter than those in Western countries. Differences between Japanese and Western guidelines may impact the detection rate and prediction of AF via ICMs in patients with CS. Available data on Japanese patients are limited to small retrospective studies. Furthermore, additional information about AF detection, including the number of episodes, cumulative episode duration, anticoagulation initiation (type and dose of regimen and time of initiation), rate of catheter ablation, role of atrial cardiomyopathy, and stroke recurrence (time of recurrence and cause of the recurrent event), was not provided in the vast majority of previously published studies. In this study, we aim to identify the proportion and timing of AF detection and risk stratification criteria in patients with CS in real-world settings in Japan. This is a multicenter, prospective, observational study that aims to use ICMs to evaluate the proportion, timing, and characteristics of AF detection in patients diagnosed with CS. We will investigate the first detection of AF within the initial 6, 12, and 24 months of follow-up after ICM implantation. Patient characteristics, laboratory data, atrial cardiomyopathy markers, serial magnetic resonance imaging findings at baseline, 6, 12, and 24 months after ICM implantation, electrocardiogram readings, transesophageal echocardiography findings, cognitive status, stroke recurrence, and functional outcomes will be compared between patients with AF and patients without AF. Furthermore, we will obtain additional information regarding the number of AF episodes, duration of cumulative AF episodes, and time of anticoagulation initiation. Study recruitment began in February 2020, and thus far, 213 patients have provided written informed consent and are currently in the follow-up phase. The last recruited participant (May 2021) will have completed the 24-month follow-up in May 2023. The main results are expected to be submitted for publication in 2023. The findings of this study will help identify AF markers and generate a risk scoring system with a novel and superior screening algorithm for occult AF detection while identifying candidates for ICM implantation and aiding the development of diagnostic criteria for CS in Japan. UMIN Clinical Trial Registry UMIN000039809; https://tinyurl.com/3jaewe6a. DERR1-10.2196/39307.

Reducing Gadolinium Exposure in Patients Undergoing Monitoring for Meningiomas.

Background Due to the non-malignant and slow-growing nature of many meningiomas, surveillance with serial magnetic resonance imaging (MRI) serves as an acceptable management plan. However, repeated imaging with gold-standard contrast-based studies may lead to contrast-associated adverse effects. Non-gadolinium T2 sequences may serve as a suitable alternative without the risk of adverse effects of contrast. Thus, this study sought to investigate the agreement between post-contrast T1 and non-gadolinium T2 MRI sequences in the measurement of meningioma growth. Methodology The Virginia Commonwealth University School of Medicine (VCU SOM) brain tumor database was used to create a cohort of meningioma patients and determine the number of patients who had T1 post-contrast imaging accompanied by readily measurable imaging from either T2 fast spin echo (FSE) or T2 fluid-attenuated inversion recovery (FLAIR) sequences. Measurements of the largest axial and perpendicular diameters of each tumor were conducted by two independent observers using T1 post-contrast, T2 FSE, and T2 FLAIR imaging series.Lin's concordance correlation coefficient (CCC) was calculated to assess inter-rater reliability between observers and agreement between measurements of tumor diameter among the different imaging sequences. Results In total, 33 patients (average age = 72.1 ± 12.9 years, 90% female) with meningiomas were extracted from our database, with 22 (66.7%) undergoing T1 post-contrast imaging accompanied with readily measurable imaging from T2 FSE and/or T2 FLAIR sequences. The inter-rater reliability between the measurements of T1 axial and perpendicular diameters was 0.96 (95% confidence interval (CI) = 0.92-0.98) and 0.92 (95% CI = 0.83-0.97), respectively. The inter-rater reliability between the measurements of T2 axial perpendicular diameters was 0.93 (95% = CI 0.92-0.97) and 0.89 (95% CI = 0.74-0.95), respectively. The agreements between the measurement of T1 and T2 FSE axial diameter by each observer were 0.97 (95% CI = 0.93-0.98) and 0.92 (95% CI = 0.81-0.97). The agreements between the measurements of T1 and T2 FSE perpendicular diameter measurements by each observer were 0.98 (95% CI = 0.95-0.99) and 0.88 (95% CI = 0.73-0.95). Conclusions Two-thirds of our patients had meningiomas that were readily measurable on either T2 FSE or T2 FLAIR sequences. Additionally, there was excellent inter-rater reliability between the observers in our study as well as an agreement between individual measurements of T1 post-contrast and T2 FSE tumor diameters. These findings suggest that T2 FSE may serve as a safe and similarly effective surveillance method for the long-term management of meningioma patients.

Quantification approaches for magnetic resonance imaging following intravenous gadolinium injection: A window into brain-wide glymphatic function.

The glymphatic system is a brain-wide network of perivascular pathways along which cerebrospinal fluid and interstitial fluid rapidly exchange, facilitating solute and waste clearance from the brain parenchyma. The characterization of this exchange process in humans has relied primarily upon serial magnetic resonance imaging following intrathecal gadolinium-based contrast agent injection. However, less invasive approaches are needed. Here, we administered a gadolinium-based contrast agent intravenously in eight healthy participants and acquired magnetic resonance imaging scans prior to and 30, 90, 180, and 360 min post contrast injection. Using a region-of-interest approach, we observed that peripheral tissues and blood vessels exhibited high enhancement at 30 min after contrast administration, likely reflecting vascular and peripheral interstitial distribution of the gadolinium-based contrast agent. Ventricular, grey matter and white matter enhancement peaked at 90 min, declining thereafter. Using k-means clustering, we identify distinct distribution volumes reflecting the leptomeningeal perivascular network, superficial grey matter and deep grey/white matter that exhibit a sequential enhancement pattern consistent with parenchymal contrast enhancement via the subarachnoid cerebrospinal fluid compartment. We also outline the importance of correcting for (otherwise automatic) autoscaling of signal intensities, which could potentially lead to misinterpretation of gadolinium-based contrast agent distribution kinetics. In summary, we visualize and quantify delayed tissue enhancement following intravenous administration of gadolinium-based contrast agent in healthy human participants.

Adjuvant multimodal treatment for spinal intradural extramedullary capillary hemangioma with subpial growth: illustrative case.

Spinal intradural extramedullary capillary hemangiomas are rare vascular lesions. Although total resection is the first treatment, the efficacy of adjuvant therapies, such as steroid or radiation therapy, has not been investigated. A 74-year-old man presented with progressive back pain, gait disturbance, and left chest pain. Spinal magnetic resonance imaging (MRI) revealed an intradural extramedullary lesion at the middle thoracic level. Preoperatively, systemic steroid administration improved his chest pain and reduced the tumor size. The authors performed tumor extirpation. Because the tumor strongly adhered to the pia matter, in short, the tumor accompanied with partial subpial growth, subtotal resection was performed, leaving a thin layer of the tumor. A pathological examination revealed capillary hemangioma. His gait disturbance showed rapid improvement. Stereotactic cyber knife treatment was performed for the residual tumor at 1 month after the operation. Serial MRI showed a gradual decrease in the tumor size and no recurrence at 2 years after the operation. When a tumor adheres to the spinal cord or nerve root, immoderate total resection should not be performed to avoid exacerbating the clinical symptoms. Adjuvant therapies, such as a systemic steroid administration or radiation therapy, may provide satisfactory control of spinal capillary hemangiomas.

Evolution of Magnetic Resonance Imaging Lesions at the Sacroiliac Joints During and After Pregnancy by Serial Magnetic Resonance Imaging From Gestational Week Twenty to Twelve Months Postpartum.

Sacroiliac (SI) joint magnetic resonance imaging (MRI) findings simulating sacroiliitis related to axial spondyloarthritis (SpA) may occur in women before and after birth. This study was undertaken to explore the prevalence, evolution, and topography of SI joint MRI lesions in pregnant and postpartum women. A prospective cohort study included 103 first-time mothers who underwent up to 5 serial SI joint MRI between gestational week 20 and 12 months postpartum. After calibration, 3 assessors independently evaluated bone marrow edema (BME), including sacroiliitis according to the Assessment of SpondyloArthritis international Society (ASAS), as well as structural lesions, using the Spondyloarthritis Research Consortium of Canada (SPARCC) and a novel 2-plane assessment method. BME was frequent both during pregnancy and the postpartum period, peaking at 3 months postpartum with a prevalence of 69% (SPARCC) and 80% (2-plane method), but still present in 54% (SPARCC) and 58% (2-plane method) of subjects at 12 months postpartum. At 12 months postpartum, sacroiliitis according to the current ASAS definition was met in 41%, while 21% and 14% of women fulfilled the newly proposed ASAS MRI thresholds for active and structural SI joint lesions, respectively. BME clustered in the anterior middle joint portions at all time points, and ligamentous BME was rare. At 12 months postpartum, SPARCC erosion scores ≥3 (ASAS threshold) were observed in only 2.8% of women. At 12 months postpartum, 41% of women met the current ASAS sacroiliitis definition, which may result in false-positive assignments of axial SpA diagnosis in postpartum women with back pain. The topographical BME distribution and virtually absent erosions (ASAS threshold) at 12 months postpartum may help discriminate postpartum strain-related conditions from axial SpA-related sacroiliitis.

Abstract SY30-03: Composing each patient’s equation: Unraveling brain tumor complexity by integrating multi-regional image-localized biopsies

Abstract Glioblastoma is a uniquely challenging and aggressive cancer that is practically considered uniformly fatal. This aggressiveness is driven by heterogeneity between and within patients and the diffuse invasion of tumor cells deep into the normal appearing brain tissue surrounding the frank tumor abnormality. Mathematical neuro-oncology (MNO) is a burgeoning field that seeks to bring together individual patient data (like patient imaging, tissue biopsies etc) to tune mathematical models that accurately predict and quantify response to treatments for each patient. These mathematical models use both mechanistic “weather forecasting” methods and artificial intelligence pattern recognition methods. Ultimately, these models form the basis of modern "precision medicine" approaches to tailor therapy in a patient-specific manner. These models can be used to overcome the limited ability of imaging to accurately detect tumor cells, improve prognostic predictions, stratify patients, and assess treatment response in silico in the construction of effective clinical trials and treatment protocols, thus accelerating the pace of clinical research. This presentation will focus on the growing translation of MNO to clinical neuro-oncology highlighting burgeoning insights into sex differences in tumor incidence, outcomes, and response to therapy. Specifically, I will discuss 1) use of our 4,500+ patient cohorts of 100,000+ annotated serial MR imaging data to develop digital twins accurately predict response and outcomes in patients and 2) our unique collection of 1000+ image-localized biopsies across nearly 200 patients to detect sex-distinct patterns of mapping between regional imaging features and underlying regional tumor biology. We will demonstrate the value of these novel combined resources in predicting response to treatment for EGFR-targeted therapies in 3 clinical trials and differentiating response to novel dendritic cells vaccines and CAR T-cell therapies in 2 additional clinical trials. Taken together, these complimentary approaches provide a platform to incorporate inter- and intra- tumoral heterogeneity into accurate predictive models that advance precision oncology for glioblastoma patients. Citation Format: Kristin R. Swanson. Composing each patient’s equation: Unraveling brain tumor complexity by integrating multi-regional image-localized biopsies. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr SY30-03.

Surgical approach to the treatment of pituicytoma. Report of five cases and a literature review

BackgroundPituicytoma (PTs) is a rare tumor of the sella and suprasellar region, derived from the pituicytes of the neurohypophysis, having distinct histological characteristics of glial neoplasms. We reported, the clinical data, neuroimaging studies, surgical approaches and pathology in five patients with PTs and also, we reviewed the literature. MethodsRetrospective chart from five consecutive patients with PTs treated at one University Hospital from 2016 to 2021 were reviewed. In addition, we conducted a search in PubMed/Medline databases using the term “Pituicytoma”. Data regarding age, gender, pathological findings, and treatment modality applied were extracted. ResultsAll patients were female, aged 29–63, complaining of headaches, visual loss and field defects, dizziness and normal or abnormal levels of circulating pituitary hormones. Magnetic Resonance Imaging (MRI) showed in all patients a sellar and suprasellar mass, which was removed through an endoscopic transsphenoidal approach. Our third patient had a subtotal resection followed by close observation. Histopathology showed a glial non-infiltrative tumors with spindle cells, and a final diagnosis of pituicytoma was made. After surgery, visual field defects in all patients were normalized, and in two patients normal levels of plasma hormones were restored. After a mean of three years follow-up, the patients were managed post-operatively through close clinical observation and serial MRI. None of the patients had recurrence of the disease. ConclusionPTs is a rare glial tumor of the sellar and suprasellar region that arises from neurohypophyseal pituicytes. Disease control may be achieved by total excision.

Brain magnetic resonance imaging in the DE50-MD dog model of Duchenne muscular dystrophy reveals regional reductions in cerebral gray matter

BackgroundDuchenne muscular dystrophy is a X-linked disease characterized by severe and progressive muscle weakness, alongside cognitive impairment and a range of neurobehavioral disorders secondary to brain dystrophin deficiency. Duchenne muscular dystrophy patients have reduced cerebral gray matter and altered white matter ultrastructure (detected by magnetic resonance imaging) compared to age-matched controls.MethodsWe studied the DE50-MD canine model of Duchenne muscular dystrophy, which is deficient in full length brain dystrophin (Dp427) isoforms and has a neurocognitive phenotype. Eight DE50-MD and 6 age-matched littermate wild type male dogs underwent serial brain magnetic resonance imaging from 14 to 33 months of age.ResultsReduced regional gray matter was detected in DE50-MD dogs compared with wildtype, including the piriform lobe, hippocampus and cingulate gyrus. Lateral ventricle volume was larger in DE50-MD dogs. Differences did not progress over time. White matter volume did not differ between DE50-MD and wildtype dogs. There was no difference in brain nor cranial vault volume between DE50-MD and wildtype dogs.ConclusionDystrophin deficiency in the canine brain results in structural changes that likely contribute to the neurocognitive phenotype.

PET imaging characteristics of neuromuscular choristoma and associated desmoid-type fibromatosis.

Neuromuscular choristoma (NMC) is a rare peripheral nerve lesion characterized by abnormal presence of muscle within nerve. Associated desmoid-type fibromatosis (NMC-DTF) often develops. We report 18F-fluorodeoxyglucose positron emission tomography (FDG PET) characteristics of NMC and NMC-DTF and propose that increased FDG activity within NMCs may be associated with subclinical NMC-DTF or NMC-DTF "precursor" tissue. Our institutional database was searched for all NMC cases. Inclusion criteria were 1) confirmed diagnosis of NMC with or without biopsy, and 2) available PET and MRI studies. PET data included SUVmax and SUVmean of NMCs, contralateral limb normal skeletal muscle and unaffected nerves, and SUVmax of NMC-DTF if present. SUV values were compared using paired t-test. A p value of < 0.05 was considered statistically significant. Our cohort consisted of 9 patients with NMC, 8 cases involving sciatic nerve and 1 of brachial plexus. On PET imaging, all NMC-affected nerve segments showed significantly higher FDG uptake (SUVmax/mean) compared to both contralateral normal nerve and normal skeletal muscle (all P < 0.05). Similar to sporadic DTF, NMC-DTF was highly FDG-avid (average SUVmax of 4.2). SUVmax in NMC with or without concurrent NMC-DTF did not differ (p = 0.76). Within NMC-affected nerve segment, FDG activity was relatively higher in areas with low T1/T2 MR signal. All NMCs were more FDG avid compared to both normal skeletal muscle and contralateral unaffected nerve, arguing against the presence of heterotopic muscle in NMC asthe source of FDG avidity. FDG avidity within NMC may reflect subclinical NMC-DTF or a precursor lesion, as NMC-DTF are highly FDG-avid, and the highest regions of FDG avidity in NMC occurred in regions with MR characteristics associated with NMC-DTF (i.e., lower T1/T2 signal). We believe that the integration of FDG PET with serial MR imaging in patient follow up will clarify its utility in both detection and surveillance of NMC-DTF.

Teach an old dog new tricks: Meningoencephalitis of unknown origin (MUO) in Australian shepherd dogs

AbstractMeningoencephalitis of unknown origin is mostly considered a disease of young small dogs and terrier breeds, while older dogs presenting with clinical signs of deteriorating encephalopathy are more commonly diagnosed with intracranial neoplasia. In this case series, three Australian shepherd dogs, 7, 10 and 11 years old, were diagnosed with meningoencephalitis of unknown origin; with serial magnetic resonance imaging in two dogs and postmortem examination in one dog. Follow‐up magnetic resonance imaging examination after 4 months showed complete resolution of magnetic resonance imaging abnormalities in one dog treated with prednisolone. The other dog had a recurrence of clinical signs and multifocal de novo lesions noted in magnetic resonance imaging done at 23 months after diagnosis and tapering of prednisolone. In older dogs, a diagnosis of intracranial neoplasia should not be assumed based on clinical signs of deteriorating encephalopathy alone, and meningoencephalitis of unknown origin should be on the differential list. Older dogs diagnosed with meningoencephalitis of unknown origin can have good outcomes with immunomodulatory therapy.

Breast Cancer Growth on Serial MRI: Volume Doubling Time Based on 3-Dimensional Tumor Volume Assessment.

The volume doubling time (VDT) of breast cancer was most frequently calculated using the two-dimensional (2D) diameter, which is not reliable for irregular tumors. It was rarely investigated using three-dimensional (3D) imaging with tumor volume on serial magnetic resonance imaging (MRI). To investigate the VDT of breast cancer using 3D tumor volume assessment on serial breast MRIs. Retrospective. Sixty women (age at diagnosis: 57 ± 10 years) with breast cancer, assessed by two or more breast MRI examinations. The median interval time was 791 days (range: 70-3654 days). 3-T, fast spin-echo T2-weighted imaging (T2WI), single-shot echo-planar diffusion-weighted imaging (DWI), and gradient echo dynamic contrast-enhanced imaging. Three radiologists independently reviewed the morphological, DWI, and T2WI features of lesions. The whole tumor was segmented to measure the volume on contrast-enhanced images. The exponential growth model was fitted in the 11 patients with at least three MRI examinations. The VDT of breast cancer was calculated using the modified Schwartz equation. Mann-Whitney U test, Kruskal-Wallis test, Chi-squared test, intraclass correlation coefficients, and Fleiss kappa coefficients. A P-value <0.05 was considered statistically significant. The exponential growth model was evaluated using the adjusted R2 and root mean square error (RMSE). The median tumor diameter was 9.7 mm and 15.2 mm on the initial and final MRI, respectively. The median adjusted R2 and RMSE of the 11 exponential models were 0.97 and 15.8, respectively. The median VDT was 540 days (range: 68-2424 days). For invasive ductal carcinoma (N=33), the median VDT of the non-luminal type was shorter than that of the luminal type (178 days vs. 478 days). On initial MRI, breast cancer manifesting as a focus or mass lesion showed a shorter VDT than that of a non-mass enhancement (NME) lesion (median VDT: 426 days vs. 665 days). A shorter VDT was observed in breast cancer manifesting as focus or mass as compared to an NME lesion. 3 TECHNICAL EFFICACY: Stage 2.

Abstract P4-07-40: Magnetic resonance imaging (MRI) and clinicopathological analysis of triple-negative breast cancer (TNBC) patients (pts) treated with primary anthracyclines(A)/taxanes(TX)-based chemotherapy

Abstract Background Radiological complete response (CR-MRI) to neoadjuvant chemotherapy (NAC) by MRI predicts pathologic complete response (pCR) rates in pts with TNBC treated preoperatively with A/TX-based regimens and in some studies, it correlates with disease-free survival (DFS). The main aim of this study was to assess the relevance of the MRI response to primary chemotherapy associated with clinical stage and HER2 expression (Zero vs Low), in a cohort of 143 TNBC pts treated with A and TX +/- carboplatin (CP) in the NAC setting. Methods Retrospective study of pts treated with NAC for TNBC between January 2002 and June 2021, who underwent MRI to assess tumour response before NAC, after 4 cycles of anthracycline and cyclophosphamide (AC) and after TX. Survival analysis was based on the Kaplan-Meier and survival curves were compared using the log-rank test. A p value of less than 0.05 was considered as statistically significant. Results A total of 143 TNBC pts with a median age of 52 years; 7, 63 and 73 pts had stage I, II and III disease, respectively. The NAC regimen consisted in 117 pts 4 cycles of AC followed by TX and in 24 pts the same adding CP (in 21 pts with non-CR-MRI, 2 with CR-MRI and 1 without MRI after AC). PCR was observed in 41%. Of 30 pts with CR-MRI after AC, 83% obtain a pCR (p&amp;lt; 0.001), and of 52 pts with CR-MRI at the end of NAC, 70.7% obtain a pCR (p&amp;lt; 0,001) of which 90% had a CR-MRI after AC. Adding CP increased pCR by 6% (p=0.564). According HER2-zero vs low expression, the pCR was 38% and 47% respectively, with no significant differences. With a median follow-up of 60 months, 34% recurred and 16% died of TNBC. In pts with pCR, the DFS at 5 years (y) was 96% and 47% for pts without pCR (p&amp;lt; 0.001), with a DFS of 91% if CR-MRI at the end of NAC and 48% if non-CR-MRI (p&amp;lt; 0.001). In HER2-Zero tumours the DFS at 5 y was 64% vs 66% in HER-2 low. Interestingly, overall survival (OS) at 5 y was 72% in HER2-Zero and 84% in HER2-low (p=0.080). Conclusions Performing serial MRI in the course of NAC in TNBC may be a reliable indicator of pCR, adding platinum to TX in pts with CR-MRI may increase pCR rate. HER2-Zero expression in TNBC, seems to confer worse OS rates. Citation Format: Marina Sierra Boada, Luis Antonio Fernandez, Elsa Dalmau, Gemma Llort, Maria Marin, Pablo Andreu, Natalia Lopez, Carla Climent, Marta Rodriguez, Sandra Soriano, Miquel Angel Segui. Magnetic resonance imaging (MRI) and clinicopathological analysis of triple-negative breast cancer (TNBC) patients (pts) treated with primary anthracyclines(A)/taxanes(TX)-based chemotherapy. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-40.

Long-Term Changes in the Size of Pituitary Microadenomas.

The estimated prevalence of pituitary lesions is 10% to 38.5% in radiologic studies. However, how frequently these incidental lesions should be monitored by serial pituitary magnetic resonance imaging (MRI) remains unclear. To evaluate changes in pituitary microadenomas over time. Retrospective, longitudinal cohort study. Mass General Brigham, Boston, Massachusetts. Evidence of pituitary microadenoma from MRI. Dimensions of pituitary microadenomas. During the study period (from 2003 to 2021), 414 patients with pituitary microadenomas were identified. Of the 177 patients who had more than 1 MRI, 78 had no change in the size of the microadenoma over time, 49 had an increase in size, 34 had a decrease in size, and 16 had both an increase and decrease in size. By linear mixed model analysis, the estimated slope was 0.016 mm/y (95% CI, -0.037 to 0.069). In the subgroup analysis, pituitary adenomas with a baseline size of 4 mm or less tended to increase in size. The estimated slope was 0.09 mm/y (CI, 0.020 to 0.161). In contrast, in the subgroup with baseline tumor size greater than 4 mm, the size tended to decrease. The estimated slope was -0.063 mm/y (CI, -0.141 to 0.015). Retrospective cohort, some patients were lost to follow-up for unknown reasons, and data were limited to local large institutions. During the study period, approximately two thirds of the microadenomas remained unchanged or decreased in size. The growth, if any, was slow. These findings suggest that less frequent pituitary MRI surveillance for patients with incidental pituitary microadenomas may be safe. None.

Radiation necrosis and therapeutic outcomes in patients treated with linear accelerator-based hypofractionated stereotactic radiosurgery for intact intracranial metastases.

Balancing disease control and treatment-related toxicities can be challenging when treating higher-risk brain metastases (BMs) that are larger in size or eloquent anatomical locations. Hypofractionated stereotactic radiosurgery (hfSRS) is expected to offer superior or equal efficacy with lower toxicity profile compared with single-fraction SRS (sfSRS). We report the efficacy and toxicity profiles of hfSRS in a consecutive cohort of patients to support this predicted benefit from hfSRS for high-risk BMs. We retrospectively analysed 185 consecutive individual lesions from 152 patients with intact BMs treated with hfSRS between 1 July 2016 and 31 October 2019 and followed up to 30 April 2022 with serial brain magnetic resonance imaging (MRI). The primary endpoint was the event of radiation necrosis (RN). Local control (LC) rate and distant brain failure (DBF) were reported as secondary outcomes. Kaplan-Meier method was used to report the cumulative incidence of RN and overall survival and the incidence of DBF. Potential risk factors for RN were assessed using univariable Cox regression analysis. The median follow-up was 38.0months, and the median survival post-SRS was 9.5 months. The cumulative incidence rate of RN was 13.2% (95% CI: 7.0-24.7%), and 18.1% of patients with confirmed RN were symptomatic. Higher mean dose delivered to planning target volume (PTV) (HR 1.22, 95% CI: 1.05-1.42, P=0.01), higher mean BED10 (biological equivalent dose assuming a tissue ratio of 10) (HR 1.12, 95% CI: 1.04-1.2, P <0.001), and higher mean BED2 (HR 1.02, 95% CI: 1-1.04, P=0.04) delivered to the lesion was associated with increased risk of RN. LC rate was 86% and the cumulative incidence of DBF was 36% with a median onset of 28.4 months. Our results support the predicted radiobiological benefit of the use of hfSRS in high-risk BMs to limit treatment-related toxicity with low risk for symptomatic RN comparable with lower risk population receiving sfSRS while achieving satisfactory local disease control.

Modifiable vascular risk factors in patients with cerebral and spinal cavernous malformations: a complete 10-year follow-up study.

The aim was to investigate the effect of modifiable vascular risk factors on the risk of first and recurrent bleeding for patients with a cavernous malformation (CM) of the central nervous system (CNS) over a 10-year period. A retrospective review of our CM institutional database was performed spanning from 2003 to 2021. The inclusion criteria were non-missing serial magnetic resonance imaging studies and clinical baseline metrics such as vascular risk factors. The exclusion criteria were patients who underwent surgical CM removal and patients with less than a decade of follow-up. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative risk (10 years) of hemorrhage. Eighty-nine patients with a CM of the CNS were included. Our results showed a non-significant increased risk of hemorrhage during 10 years of follow-up in patients using nicotine (hazard ratio 2.11, 95% confidence interval 0.86-5.21) and in patients with diabetes (hazard ratio 3.25, 95% confidence interval 0.71-14.81). For the presence of modifiable vascular risk factors at study baseline different cumulative 10-year risks of bleeding were observed: arterial hypertension 42.9% (18.8%-70.4%); diabetes 66.7% (12.5%-98.2%); hyperlipidemia 30% (8.1%-64.6%); active nicotine abuse 50% (24.1%-76%); and obesity 22.2% (4%-59.8%). Overall cumulative (10-year) hemorrhage risk was 30.3% (21.3%-41.1%). The probability of hemorrhage in untreated CNS CM patients increases progressively within a decade of follow-up. None of the modifiable vascular risk factors showed strong indication for an influence on hemorrhage risk, but our findings may suggest a more aggressive course in patients with active nicotine abuse or suffering from diabetes.

T cell-independent eradication of experimental glioma by intravenous TLR7/8-agonist-loaded nanoparticles

Glioblastoma, the most common and aggressive primary brain tumor type, is considered an immunologically “cold” tumor with sparse infiltration by adaptive immune cells. Immunosuppressive tumor-associated myeloid cells are drivers of tumor progression. Therefore, targeting and reprogramming intratumoral myeloid cells is an appealing therapeutic strategy. Here, we investigate a β-cyclodextrin nanoparticle (CDNP) formulation encapsulating the Toll-like receptor 7 and 8 (TLR7/8) agonist R848 (CDNP-R848) to reprogram myeloid cells in the glioma microenvironment. We show that intravenous monotherapy with CDNP-R848 induces regression of established syngeneic experimental glioma, resulting in increased survival rates compared with unloaded CDNP controls. Mechanistically, CDNP-R848 treatment reshapes the immunosuppressive tumor microenvironment and orchestrates tumor clearing by pro-inflammatory tumor-associated myeloid cells, independently of T cells and NK cells. Using serial magnetic resonance imaging, we identify a radiomic signature in response to CDNP-R848 treatment and ultrasmall superparamagnetic iron oxide (USPIO) imaging reveals that immunosuppressive macrophage recruitment is reduced by CDNP-R848. In conclusion, CDNP-R848 induces tumor regression in experimental glioma by targeting blood-borne macrophages without requiring adaptive immunity.