Serial MRI Research Articles

Background: Ulcer-like projections (ULPs) in aortic dissections are linked with aortic expansion, but predicting the progression is difficult. While earlier studies used computational fluid dynamics, 4D flow MRI allows direct in vivo measurement and visualization of complex blood flow dynamics. Hypothesis: We hypothesized that specific intra-ULP flow patterns, including vortex flow and wall shear stress (WSS) elevation, directly measured by 4D flow MRI, may predict short-term aortic expansion. Methods: We prospectively examined patients with ULP-type aortic dissection. Using 4D flow MRI, we assessed the intra-ULP hemodynamics, obtaining direct in vivo measurements of time-resolved 3D blood flow velocities. The intra-ULP vortex flow was detected using streamlines. WSS distribution on the ULP wall was analyzed, with localized WSS elevation as a key parameter. Patients were followed-up with serial CT or 4D flow MRI to monitor the aortic diameter. The primary endpoint was aortic expansion. Results: Nine patients with ULPs (mean age: 62.4 ± 10.8 years; 77.8% male;)—six with type A dissection and three with type B dissection—were analyzed. Four patients (44.4%; one with type A dissection and three with type B dissection) had vortex flow within the ULP and associated localized WSS elevation. All four patients showed rapid aortic expansion (mean increase: 7.25 ± 1.71 mm) between onset and follow-up CT/MRI over a short period (mean: 4.0 ± 5.4 months; median [range]: 1.5 [1-2] months). Three patients subsequently received thoracic endovascular aortic repair and one underwent total arch replacement. The remaining five patients (55.6%; all with Type A dissection) with no vortex flow and no remarkably localized WSS elevation within the ULP showed no significant aortic expansion (mean increase: 3.0 ± 1.58 mm) over a long period (mean: 41.0 ± 25.0 months; median [range]: 55 [3-61] months); all were managed conservatively. Intra-ULP vortex flow with localized WSS elevation based on direct flow measurements was significantly associated with short-term aortic expansion (p<0.05). Conclusion: Vortex flow within ULPs and localized WSS elevation, directly measured and visualized using 4D flow MRI, are strong predictors of short-term aortic expansion in patients with ULP-type aortic dissection.

Background Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive and fatal neurodegenerative disorder. Early diagnosis remains challenging due to nonspecific initial symptoms. Although electroencephalography (EEG) is a key diagnostic tool, particularly through the detection of periodic sharp wave complexes (PSWCs), the longitudinal evolution of EEG features and their correlation with clinical and neuroimaging progression are not fully characterized. Methods This retrospective cohort study analyzed 37 patients diagnosed with probable and very probable sCJD according to the 2021 Chinese diagnostic guidelines. All patients underwent at least one EEG examination. One representative patient was followed for 23 weeks with serial EEG and MRI studies to document dynamic electrophysiological and structural changes. EEG background activity was graded as mild, moderate, or severe, and PSWCs were identified based on standardized criteria. MRI analyses focused on the spatial and temporal progression of hyperintense lesions on DWI and FLAIR sequences. Results Among the 37 patients, 46% underwent initial EEG within 1 month of symptom onset, and 49% exhibited severe background abnormalities. PSWCs were present in 84% of patients at first EEG, with a high prevalence (82%) even in those examined within 4 weeks of onset. Longitudinal analysis in the index case revealed a progressive EEG deterioration: from slowed and disorganized background rhythms and emerging triphasic waves at 8 weeks, to widespread PSWCs with increasing periodicity (9–16 weeks), and finally to a burst-suppression pattern near electrical silence by week 23. Concurrent MRI showed a parallel expansion of hyperintense lesions from unilateral cortical and basal ganglia regions to bilateral involvement, closely correlated with the EEG progression. Statistical analysis showed no significant correlation between survival time and age, time to first EEG, CSF 14–3-3 protein status, or initial EEG background grade. Furthermore, neither the presence of typical PSWCs nor the severity of background activity was associated with survival outcomes. Conclusion EEG, especially the early and highly prevalent presence of PSWCs, offers high diagnostic value in sCJD but does not serve as prognostic predictors. The close correlation between EEG decline and MRI progression supports multimodal monitoring. Serial EEG should be integrated into sCJD diagnosis and follow-up.

Apparent Diffusion Coefficient MRI as a Predictive Biomarker for Hypoxia, Treatment De-escalation, and Recurrence in HPV-Associated Oropharyngeal Cancer.

Abstract Disclosure: Y. Park: None. D. McArdle: None. F. Gaillard: None. R. Ly: None. J. King: None. A.S. Trigos: None. A. Shen: None. C.J. Yates: None. IntroductionSteroidogenic factor 1 (SF1) immunohistochemistry (IHC) has led to an increased detection of gonadotroph adenomas1 and SF1+/luteinising hormone (LH)-/follicular stimulating hormone (FSH)- gonadotroph adenomas are the most prevalent histological gonadotroph adenoma subtype.2 Clinical heterogeneity of gonadotroph adenoma has been suggested between the LH-/FSH+, LH+/FSH- and FSH+/LH+ subtypes.3 However, clinical significance of the SF1+/LH-/FSH- histological subtype is unknown. Methods: In a retrospective matched cohort study at an Australian tertiary hospital, inpatients diagnosed with pituitary tumours between 1st January 2021 and 3rd July 2024 were screened using ICD codes and an established pituitary database. One SF1+/LH-/FSH- gonadotroph adenoma was matched per other gonadotroph adenoma histological subtypes by age and sex. Pre-operative MRI was analysed for tumour volume, invasiveness, texture analysis, and apparent diffusion coefficient (ADC) values. Serial MRI at 3-6 months post-operatively and the most recent available were analyzed. Clinical (including reproductive hormones and reoperation) and IHC data were collected. Results: Of 70 patients with confirmed gonadotroph adenomas, one SF1+/LH-/FSH- gonadotroph adenoma (n=13) was matched with 13 other gonadotroph adenoma histological subtypes (SF1+/LH-/FSH+ (n=5)/SF1+/LH+/FSH- (n=4)/SF1+/LH+/FSH+ (n=4). FSH+ gonadotroph adenomas (SF1+/LH-/FSH+ and SF1+/LH+/FSH+, n=9) had higher ADC (892 [786-943] vs. 664 [592-719] mm2/s; p=0.007) and achieved more GTR (50% vs. 0%; p=0.048) compared to FSH- gonadotroph adenomas (SF1+/LH-/FSH- and SF1+/LH+/FSH-, n=14). There were no differences in invasion (Knosp grade ≥ 3 or sphenoid sinus invasion) (p=0.48) or reoperation (p=0.57) between the two groups. There were no differences in tumour volume (p=0.38), T1 intensity (p=0.43), T2 intensity (p=0.21), Knosp grade (p=0.94), sphenoid sinus invasion (p=0.74), hypopituitarism (p=0.28), use of sex hormone replacement therapy (p=0.37), estrogen receptor alpha IHC (p=0.14), Ki67 (p=0.81) and reoperation (p=0.79) across the four histological subtypes. All tumours had a suprasellar extension. On dynamic contrast-enhanced sequences, delayed (n=14/16) and heterogeneous enhancement (n=19/24) relative to normal pituitary were common. Serum LH and FSH levels were not associated with LH (p=0.51) and FSH IHC (p=0.78) respectively. Conclusions: Our small pilot study demonstrated FSH+ gonadotroph adenomas have greater MRI apparent diffusion coefficients and GTR rates than FSH- gonadotroph adenomas, however, without differences in invasion or reoperation. High ADC values have been associated with a reduced risk of recurrence4 and invasiveness5 of pituitary adenomas. Larger studies are warranted to evaluate ADC of gonadotroph adenoma histological subtypes and its potential clinical significance. Presentation: Saturday, July 12, 2025

Disclosure: C. Rizk: None. G. Sydney: None. P. Gopal: None. S. Omay: None. P. Balasubramanian: None.Background: Ectopic salivary tissue within the sella is rare and mostly asymptomatic. Preoperative diagnosis is often challenging as they mimic pituitary neoplasms and the diagnosis is typically made after resection or biopsy. We present a case of ectopic intrasellar salivary gland tissue confirmed on histopathology in a patient who was presumed to have a meningioma on her initial imaging performed for the evaluation of headache. Case Presentation: A 61-year-old female presented with 4 month history of severe bifrontal headache and bilateral upper extremity weakness. Brain MRI was performed revealing a 2.8 x 2.6 x 1.9 cm mass along the left petroclival region extending into the sella, and into the left cavernous sinus with deviation of the pituitary stalk. The MR imaging characteristics were consistent with meningioma. Endocrine biochemical evaluation was unremarkable. Given the discordance between the patient’s clinical presentation and imaging characteristics and the short duration of her symptoms, endoscopic endonasal biopsy of the sellar lesion was performed for a definitive diagnosis. Histopathology was consistent with benign seromucinous salivary gland tissue with chronic inflammatory infiltrate. To rule out metastatic disease, DOTATATE PET scan was done which showed tracer uptake within the sella and the left cavernous sinus but no other abnormality. The patient was managed conservatively with improvement in her symptoms, and the lesion has remained stable on serial MRI imaging over the last one year. Conclusion: Ectopic salivary gland tissue in the sellar region is a rare finding and is typically asymptomatic. When symptoms do occur, they are often attributed to leakage of glandular secretions leading to localized inflammation. In uncommon instances, larger lesions may cause endocrine disturbances, including hyperprolactinemia or growth hormone deficiency. Definitive diagnosis generally relies on histopathological evaluation, and the overall prognosis is excellent.Presentation: Sunday, July 13, 2025

Perinatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality, and the current standard of care, therapeutic hypothermia, provides only partial neuroprotection. This study investigates the potential of low-frequency transcranial magnetic stimulation (LF-TMS) as a novel non-pharmacological adjunct therapy by targeting a key pathological mechanism of HIE: a persistent, pathological increase in glutamatergic synaptic transmission, or hypoxic long-term potentiation (hLTP).Using a neonatal mouse model of hypoxia-ischemia, we administered a single session of LF-TMS shortly after the hypoxic event. We then evaluated its effects on synaptic function via slice electrophysiology and on brain injury volume using serial MRI. Our results show that hypoxia-ischemia induced a significant and lasting synaptic potentiation in the brain’s penumbral region. A single LF-TMS treatment successfully reduced this elevated glutamatergic response to control levels, suggesting a therapeutic mechanism similar to long-term depression (LTD) by regulating AMPA receptor redistribution.Furthermore, LF-TMS provided significant neuroprotection, as demonstrated by a reduction in the volume of the ischemic core and penumbra 48 hours after the injury. LF-TMS did not alter excitability in sham-treated mice, confirming its safety as a targeted intervention for pathological conditions without affecting normal brain function. This study provides strong evidence that LF-TMS is a promising neuroprotective strategy that acutely and subacutely mitigates brain injury in a neonatal hypoxia-ischemia model.

Accumulating evidence suggests that physical activity is associated with a better clinical and cognitive course in Parkinson disease (PD), yet whether these effects are subserved by structural brain alterations are largely unexplored. The aim of this study was to investigate whether regular physical activity associates with a reduced longitudinal rate of neurodegeneration and slower cognitive decline in PD. In this longitudinal, observational cohort study, we used data from the Parkinson's Progression Markers Initiative. We included patients with early PD who had serial assessments of regular physical activity, measured using the Physical Activity Scale for the Elderly, along with serial MRI scans from at least 2 time points over 4 years of follow-up. Regional cortical thickness and subcortical volumes were calculated using established procedures. We used multivariate linear mixed-effects models to analyze the effect of regular physical activity on the progression of MRI parameters over time. We further used mediation models with nonparametric bootstrap to test mediation effects of longitudinal structural brain changes on the association between regular physical activity and longitudinal cognitive functioning. A total of 120 patients with early PD were included (mean [SD] age = 60.8 [9.3] years; 33% women). Average regular physical activity levels over time were significantly associated with slower cortical thinning in temporoparietal cortical regions, including the lateral temporal cortex, the fusiform gyrus, the parahippocampal gyrus, and the inferior parietal cortex (p < 0.05). Regular physical activity levels over time were also associated with slower volume loss in the hippocampus and the amygdala (p < 0.05). The association of regular physical activity with slower decline in memory and attention functions was mediated by slower decreases in temporoparietal cortical thickness (βPASE-HVLT, = 0.06, p = 0.050; βPASE-SDMT = 0.04, p = 0.017) and hippocampal volume (βPASE-SDMT = 0.03, p = 0.016). Regular physical activity is associated with a slower rate of neurodegeneration in the temporoparietal cortex and limbic areas in PD, which contributes to preserved cognitive function and improved long-term outcomes. This supports regular physical activity as a key intervention to delay disease progression and improve quality of life in patients with PD.

Changes in prostate volume during prostate SBRT delivered on an MR-Linac and correlation with acute toxicity.

Primary CNS angiitis in a woman: A case report with serial MRI evaluation

Treatment response assessment in glioblastoma with GRASP DCE-MRI.

Brain parenchymal mass effect after acute intracerebral hemorrhage (ICH) causes neurologic deficits by displacing and or damaging the corticospinal tract (CST). The impact of corticospinal tract displacement (CSTD) on arm recovery and the influence of hematoma reversal on recovery are not well understood. We conducted a serial MRI study to explore these relationships. Eighteen patients with spontaneous subcortical ICH were scanned on days 2 (baseline) and 90 (90 days) of onset. We used 3D-anatomic and 2D-DTI MRI, segmenting hematoma volume (HV), perihematomal edema (PHE), and the posterior limbs of the internal capsule (PLIC) volume labeled as native space. Presegmented PLIC volumes labeled as standard PLIC were obtained by using DTI-atlas. All segmented volumes were registered on a standard T1-weighted image followed by inverse-matrix transformation. Centroid-coordinates in native and standard PLIC were determined and a change in Euclidean distance was used to assess CSTD. Additionally, we measured changes in corticospinal tract volume due to lesion load (LLCSTV). ICH severity and upper extremity impairment were assessed by using NIHSS and Fugl-Meyer Upper Extremity (FM-UE) scores. A generalized linear mixed-model was applied to analyze CSTD and volume changes. A Bayesian inference was used to determine the posterior probability (PP). The CSTD, LLCSTV, and HV were correlated with NIHSS and FM-UE scores. We enrolled 11 men and 7 women, with a mean age of 54.8 (standard deviation = 11.8). Analyses found strong support for temporal change in hematoma volume (14.8 ± 23.7 to 4.46 ± 4.99 mL) 75.5% decrease in log HV (b = -1.41, PP > 99.9%), a 64.3% decrease in NIHSS (b = -7.95, PP > 99.9%), and a 111.8% increase (25.9 ± 22.0 to 41.0 ± 22.1 mL) in FM-UE (b = 20.2, PP = 99.8%). The average ipsilesional (absolute = 10.1 ± 4.5 to 5.78 ± 2.26 mm) log CSTD decreased by 44.9% (b = -0.59, PP = 99.9%). The LLCSTV (27.8 ± 3.8 to 31.4 ± 2.8 mL) increased by 12.9% (b = 3.69, PP > 99.9%). Both ipsilesional log CSTD (b = -0.011, PP > 99.2%) and CST volume (b = 0.06, PP >99.8%), were strongly associated with arm recovery (FM-UE) substantiated by a strong association with stroke severity (NIHSS). We present a quantitative surrogate imaging marker of CSTD and its association with arm recovery after ICH.

BACKGROUND. The macrocyclic agent gadopiclenol, FDA-approved in 2022, has relatively high T1 relaxivity, allowing substantial dose reductions. OBJECTIVE. The purpose of this study was to perform an intraindividual quantitative and qualitative comparison of contrast enhancement between brain MRI examinations in pediatric patients performed using gadopiclenol (0.05 mmol/kg) and gadoterate meglumine (0.1 mmol/kg). METHODS. This retrospective study included 38 pediatric patients (mean age: 11.1 years; 25 male patients, 13 female patients) who underwent gadopiclenol-enhanced brain MRI (0.05 mmol/kg) from December 1, 2024, to March 31, 2025, and gadoterate meglumine-enhanced MRI (0.1 mmol/kg) within the prior 6 months using the same field strength and protocol. Data were separately analyzed for 3D T1-weighted (T1W) fast spin-echo (FSE), 3D T1W gradient-recalled echo (GRE), and 2D FLAIR postcontrast sequences (27, 11, and 22 patients, respectively). The contrast ratio (CR) and CNR were measured in physiologic enhancing structures (choroid plexus, pituitary, dural venous sinuses, turbinate mucosa). Two neuroradiologists identified a preferred sequence for characterizing enhancement of physiologic enhancing structures (choroid plexus, pituitary, dural venous sinuses, turbinate mucosa, dura mater) in side-by-side blinded comparisons using a Likert scale (-2 to 2). RESULTS. CR was higher for gadopiclenol than for gadoterate for the choroid plexus on 3D T1W FSE images (71.0 ± 17.8 vs 63.4 ± 37.2, p = .04) and turbinate on 3D T1W GRE images (81.7 ± 21.8 vs 58.1 ± 25.2, p = .01). The remaining comparisons of CR between the two agents were not significant (p > .05). The CNR was not significantly different between the two agents for any combination of structure and sequence (p > .05). Both readers, reader 1 (R1) and reader 2 (R2), preferred gadopiclenol on 3D T1W FSE images for the choroid plexus (R1 [mean score ± SD]: -0.4 ± 0.5, p = .005; R2: -0.5 ± 0.8, p = .02) and pituitary (R1: -0.5 ± 0.7, p < .001; R2: -0.5 ± 0.9, p = .009). R2 also preferred gadopiclenol on 3D T1W FSE images for the turbinate (mean score ± SD, -0.7 ± 0.7; p < .001). Both readers preferred gadoterate meglumine on FLAIR images for the turbinate (R1: 0.3 ± 0.5, p = .01; R2: 0.5 ± 0.8, p = .02). R2 also preferred gadoterate meglumine on FLAIR images for the choroid plexus (mean score ± SD, 0.5 ± 0.8; p = .01). Neither reader had a significant preference for either agent for the remaining combinations of structure and sequence (p > .05). CONCLUSION. The findings support use of gadopiclenol at half the standard gadolinium dose for pediatric brain MRI examinations. CLINICAL IMPACT. The use of gadopiclenol could facilitate reductions in cumulative gadolinium exposure in children requiring serial MRI examinations.

BackgroundNon-tuberculous mycobacteria (NTM) are pulmonary pathogens with increasing incidence and prevalence worldwide, with people with cystic fibrosis (pwCF) traditionally considered at high risk of disease development. The imaging assessment of NTM-pulmonary disease (NTM-PD) relies heavily on high-resolution computed tomography (HRCT). However, due to lengthy treatment regimens and the need for long-term follow-up, serial HRCT’s result in progressive exposure to ionizing radiation; a particular concern in younger people.MethodsWe performed a retrospective cohort study of patients who had undergone serial thoracic magnetic resonance imaging (tMRI) scans to monitor NTM-PD as a novel tool to image the lung with a view to creating an algorithm for the utility of tMRI in the management of NTM-PD.ResultsThirty-six patients, of which twenty-four had a diagnosis of CF, with suspected or confirmed NTM-PD underwent serial tMRI between 1st January 2013 and 30th June 2018. A total of 117 serial tMRI’s were performed (mean number per patient 3.25; range 2–6). The associated clinical impact that each serial MRI had on management, deemed as the utility of tMRI, found that all tMRI’s were classified as aiding management with 60 (51.3%) altering management. tMRI’s were more likely to alter management in the non-CF cohort than the CF cohort (69.4% vs. 43.2%). No imaging-related adverse events were reported across the 117 tMRI’s.ConclusionThis study highlights that tMRI may hold promise as a monitoring tool in NTM-PD and should be prospectively evaluated in the monitoring of individuals with NTM-PD.

Background: Pediatric high-grade glioma (pHGG) is a highly aggressive cancer with unique biology distinct from adult high-grade glioma, limiting the effectiveness of standard treatment protocols derived from adult research. Objective: The purpose of this report is to present preliminary results from an ongoing pilot study integrating spectroscopic magnetic resonance imaging (sMRI) to guide proton beam therapy and longitudinal imaging analysis in pediatric patients with high-grade glioma (pHGG). Methods: Thirteen pediatric patients under 21 years old with supratentorial WHO grade III-IV glioma underwent baseline and serial whole-brain spectroscopic MRI alongside standard structural MRIs. Radiation targets were defined using T1-weighted contrast enhanced, T2-FLAIR, and Cho/NAA ≥ 2X maps. Longitudinal analyses included voxel-level metabolic change maps and spatial overlap metrics comparing pre-proton therapy and post-. Results: Six patients had sufficient longitudinal data; five received sMRI-guided PBT. Significant positive correlation (R2 = 0.89, p < 0.0001) was observed between T2-FLAIR and Cho/NAA ≥ 2X volumes. Voxel-level difference maps of Cho/NAA and Choline revealed dynamic metabolic changes across follow-up scans. Analyzing Cho/NAA and Cho changes over time allowed differentiation between true progression and pseudoprogression, which conventional MRI alone struggles to achieve. Conclusions: Longitudinal sMRI enhanced metabolic tracking in pHGG, detects early tumor changes, and refines RT targeting beyond structural imaging. This first in-kind study highlights the potential of sMRI biomarkers in tracking treatment effects and emphasizes the complementary roles of metabolic and radiographic metrics in evaluating therapy response in pHGG.

Background: Infantile acute subdural hematoma (IASDH) and subdural hematohygroma (SDHy) have been seemingly closely related disorders, to date, however, there have been poorly elucidated concerning the etiological relationship. The present case report aimed to approach possible etiology commonly developing both disorders. Case description: A one month-old girl suffered fever associated with poor milk feeding. Because these symptoms failed to subside and the diagnosis was undefinitive, she was transiently hospitalized for sepsis workup. Head CT revealed focal enlargement of subarachnoid space (SAS), and MRI 9 days later showed benign enlargement of subarachnoid space. Two months later, however, she was noted to have generalized convulsive seizure, prompting to refer to a nearby hospital. At the emergency room, although she was alert and asymptomatic, head CT revealed acute subdural hematoma (ASDH). Ophthalmological examination failed to reveal retinal hemorrhage. MRI 9 days later disclosed disappearance of ASDH and newly developed bilateral SDHy. Her clinical course was uneventful, and follow-up CT at the age of 4 months showed enlargement of subarachnoid spaces on both frontotemporal regions and disappearance of SDHy. Discussion and conclusion: In the present case, clinical course and serial neuroimaging findings, particularly CT and MRI at the age of one month undergone as routine sepsis workup without neurological events, are invaluable to elucidate the pathological similarity between IASDH and SDHy. Second CT taken after seizure showed thin film-like ASDH associated with enlargement of SAS, typical features seen in mild-type IASDH. On the other hand, second MRI 9 days after CT revealed disappearance of ASDH, and disclosed bilateral SDHy associated with benign enlargement of subarachnoid space. This phenomenon indicates early disappearance of mild-type IASDH together with progressive enlargement of SAS probably leading to development of SDHy

Abstract Introduction: The Molecular and Imaging Response Analysis of Co-Clinical Trials (MIRACCL, https://miraccl.research.bcm.edu/ ) platform was developed beginning three years ago to support the co-clinical breast cancer RESPONSE trial at Baylor College of Medicine. The goal of MIRACCL is to enable parallel studies which apply the same protocol to patients in a clinical trial and patient-derived xenograft (PDX) cohorts. MIRACCL evaluates treatment response by electronically measuring the changes in serial MRI. The response assessments include the measurement of multiple imagine features such as apparent diffusion coefficient (ADC) and signal enhancement ratio (SER) at pre-treatment and post-treatment along with samples taken for assessment of the genomic changes.Methods: To achieve this goal, we employee the use of web-technologies to enable visual and quantitative comparison of the imaging and genomics. Investigators at Baylor College of Medicine leveraged their expertise in patient derived xenograft development and model study implementation to generate the PDX imaging dataset and collect the model samples for sequencing. The University of Texas at Austin provided centralized patient and PDX image normalization, segmentation, and analysis while the Biomedical Informatics team at Stanford University provided the image visualization tool and imaging response assessment. Due to the difference in data modalities, data sources, and temporal collection of data it was necessary to place the data within the context of the study design and provide visual and quantitative comparisons of the study outcomes for various time points. The MIRACCL features created to achieve this goal include tabular cohort annotations, a side-by-side visualization of imaging response distributions, and a comparison of the upregulated and down regulated gene expression between cohorts. One of the imaging methods deployed in MIRACCL to assess treatment response measures response by tumor longest diameter which is then categorized by RECIST. Additional imaging comparison methods include signal enhancement ratio (SER), apparent diffusion coefficient (ADC), and tumor volume. Samples for sequencing taken at pre-treatment and throughout the design of the study are used to identify gene expression changes brought about by treatment. In the Omics module of MIRACCL, the 500 most frequently upregulated and 500 down regulated genes for each cohort are displayed based on user selected time points and imaging feature of interest. A Venn diagram is generated to identify the genes which are commonly regulated in both cohorts.Results &amp; Conclusion: While these features have provided multiple methods of comparing the outcome of co-clinical trials, the research team desired to know the significance of these correlations and differences between the two cohorts. Consequently, the Analytic module was implemented in MIRACCL this past year. The analytics module focuses on two hypotheses: 1) PDX models of similar subtyping will respond in a similar manner to the patients enrolled in the trial and 2) Response can be predicted while on-treatment to determine if changes to treatment are warranted. The change in tumor quantifications from on-treatment to baseline were statistically correlated to changes in tumor quantifications from post-treatment to baseline to determine if response could be determined while currently on-treatment. The p value and r value of the spearman correlation are provided to determine the significance and clustering of the cohort. The enhancements afforded by MIRACCL’s Analytics module summarize the treatment response of the patient and PDX cohorts and effectively address the hypothesis of the REPONSE trial. MIRACCL is now available for expansion as a tool for other trials co-clinical trials. Citation Format: Heidi Dowst, Fei Zheng, Emel Alkim, Apollo McOwiti, Ram Rajaram Srinivasan, David Hormuth, Thomas Yankeelov, Daniel Rubin, Michael T. Lewis. The MIRACCL Portal for Comparing Patient and PDX Response Using Cancer Image Features and Genomics in Co-Clinical Breast Cancer Trials [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-04-17.

e16159 Background: Immune checkpoint blockade (ICB) alone or in combination with chemotherapy has demonstrated a modest survival benefit in gastroesophageal cancer patients. In other cancer, epigenetic therapies have been shown to improve effectiveness of ICB via additive antiproliferative effects, enhanced immune activation, and reversal of T-cell exhaustion. Methods: To induce esophageal adenocarcinoma (EAC), esophagojejunostomy was performed on Sprague-Dawley rats. 32 weeks postoperative, 74 animals were randomized into 8 unique groups. Animals underwent three 14-day cycles of epigenetic therapy or placebo, ± radiation. Cycles consisted of 1 week of DNA methyltransferase treatment or placebo at 0.5 mpk, then 1 week of HDAC treatment or placebo at 2 mpk. One dose of 3 mpk PD1 inhibitor (AUNP-12) or placebo was given each cycle. Safety and efficacy were evaluated via health assessments, serial MRI, immunofluorescent labeling (IF) and RNA sequencing. Results: The study showed no differences in mortality (p = 0.556) between study groups. Pre- to post-treatment mean MRI tumor volume increased by 263.1% and 90.9% in the placebo and the placebo + radiation groups, respectively. Significant tumor reduction was observed in the dual therapy groups, 84.5% and 61.8% ± radiation, respectively. Independent epigenetic and ICB treatments ± radiation exhibited a decrease in tumor volume, but to a lesser extent than the dual regimens (p = 0.0046). IF demonstrated a significant increase in CD3CD8 + T cells in all treatment groups compared to placebo (p = &lt; 0.0001). The degree of CD3CD8 + T cell intratumor infiltration was positively associated with the depth of tumor response as measured by MRI. Bulk tumor RNAseq analysis by DESeq2 revealed a modest transcriptional response, with the greatest number of differentially expressed genes occurring in epigenetic therapy (n = 113 genes) and the dual therapy ± radiation (n = 96 genes) groups. Gene set enrichment analysis of RNAseq data defined a conserved induction of interferon-related gene sets across all treatment groups. Dual therapy ± radiation revealed a pronounced downregulation of epithelial-mesenchymal transition (EMT) and hypoxia-related gene sets. Critically, interferon, EMT, and hypoxia-related gene sets were all found to have a significant association with the depth of tumor regression in response to therapy. Conclusions: This study establishes antitumor efficacy and molecular correlates associated with response for epigenetic therapy with ICB and radiation, to treat EAC. All treatment groups enhanced CD3CD8 + T-cell tumor infiltration and interferon signaling. Dual therapy ± radiation, downregulated EMT and hypoxia-related gene sets, both having a role in modulation of cancer hallmarks, including the acquisition of an immune suppressive tumor microenvironment, tumor invasion, and metastasis.

Loss of distal hand and finger control is among the most disabling consequences of stroke. Functional outcomes are typically worse when infarcts involve subcortical white matter tracts, particularly the internal capsule, yet most preclinical stroke models target cortical regions. To address this gap, we developed a non-human primate model of internal capsule infarct using stereotactically guided endothelin-1 injections to disrupt descending fibers from the primary motor cortex hand area. Serial structural and diffusion MRI, along with histology, confirmed subcortical infarcts centered on the targeted white matter region with no apparent cortical involvement. Motor function was assessed pre- and post-infarct using a joystick-based center-out task (proximal forelimb control) and a Klüver board task (distal forelimb control). Animals exhibited variable impairments in proximal function and consistent post-infarct deficits in distal function, including reduced contralesional hand use, longer retrieval time, and increased in-well digit flexions. One animal showed mild post-infarct impairment and the smallest lesion, highlighting that this model reflects inter-individual differences in infarct size and functional outcome as seen in human subcortical stroke. In contrast, the other two animals developed a compensatory wrist-extended posture on the Klüver board task by 4 weeks post-infarct, which stabilized the hand and enabled improved digit flexion. Incorporating this behavioral adaptation into statistical models improved prediction of motor performance. The observed adaptation may have drawn on spared corticospinal output pathways, allowing animals to re-engage pre-existing motor routines to perform the retrieval. While future studies may benefit from ethologically relevant tasks to further elucidate such adaptations, findings from this study recapitulate key features of human subcortical stroke, including persistent distal motor deficits and emergence of adaptive motor strategies. By combining precise lesioning, longitudinal imaging, and detailed behavioral analysis, this model provides a translationally oriented platform for studying white matter stroke mechanisms and evaluating interventions that promote functional recovery.

Differentiation of tumor progression from pseudoprogression in glioblastoma patients with GRASP DCE-MRI and DSC-MRI.

INTRODUCTION/BACKGROUNDXanthomatous hypophysitis is a rare inflammatory condition affecting the pituitary gland, characterized by the presence of lipid-laden macrophages (xanthoma cells) and chronic inflammation. CASEWe describe a 26-year-old female with a 12-year history of xanthomatous hypophysitis complicated by panhypopituitarism and diabetes insipidus. Initial presentation at age 13 years with growth failure led to transcranial tumor debulking in 2016, with histopathology confirming chronic xanthogranulomatous inflammation. Due to recurrent disease activity, she received two courses of high-dose prednisolone (2018 and 2019–2020), followed by maintenance azathioprine (initiated 2020, currently 25 mg daily). Serial MRI surveillance showed a gradual regression of the lesion over time. In July 2023, the hypothalamic lesion measured 1.3 × 0.8 × 0.8 cm, a reduction from its previous size of 1.5 × 1.3 × 1.1 cm in 2021. This regression was accompanied by decreased compression on the optic chiasm. The pituitary gland remained thinned, and the posterior pituitary bright spot is absent, consistent with long-standing structural damage. These findings suggest ongoing inflammatory control under azathioprine. Hormonal management included levothyroxine (37.5 mcg/day), sublingual desmopressin (60 mcg/day for DI), and cyclic estrogen-progestin (Progyluton). Adrenal function recovered post-steroid withdrawal, confirmed by a normal Synacthen test (peak cortisol 624 nmol/L, 2022). Complications included secondary osteoporosis (spine T-score -1.8, hip -2.5) managed with calcium/vitamin D, and microcytic anemia (Hb 9.4 g/dL, MCV 29.8 fL), likely due to iron deficiency, now treated with oral iron and folate. CONCLUSIONThis case highlights the chronic relapsing-remitting nature of xanthomatous hypophysitis, necessitating long-term immunosuppression and meticulous endocrine surveillance. The latest MRI findings (2023) confirm disease stability under azathioprine, supporting its role in preventing progression. However, residual hypothalamic involvement underscores the need for continued monitoring. A multidisciplinary approach (endocrinology, neurosurgery, rheumatology) remains essential to manage hormonal deficits, bone health, and potential disease recurrence. Future considerations include azathioprine tapering if imaging remains stable, emphasizing the importance of serial MRI in guiding therapy.