Progression of cardiac remodelling in adolescents and adults with tetralogy of Fallot: Insights from serial magnetic resonance imaging.

Predicting response to treatment and long-term disability in multiple sclerosis (MS) remains challenging. In other complex diseases, combining genetic risk variants has enabled the detection of relevant clinical endophenotypes associated with important outcomes, but this strategy has never been applied to MS. We applied unsupervised hierarchical clustering to genomic risk scores in a prospective Welsh MS cohort (n=1455) and replicated the findings in the postmortem Netherlands Brain Bank (NBB) MS (NBB-MS) cohort (n=272). Disease progression was assessed using survival analysis to determine the time to Expanded Disability Status Scale (EDSS) milestones. Three genomic clusters were identified, each with similar genetic profiles. Baseline demographics did not differ between clusters. Welsh patients in cluster 1 attained EDSS 6 and EDSS 8 significantly later than clusters 2 and 3 (by 6 years, p=3×10-3 and 13 years, p=0.02, respectively). These findings were replicated in the NBB-MS cohort (6-year delay to EDSS 6 for cluster 1 vs 2, p=0.04). Genomic clustering independently predicted disease progression (HRs 1.3-2.0, all p<0.05), beyond established risk factors. Clusters 2 and 3 showed a greater annual increase in T2 lesion load on serial MR imaging (p=0.04). In cluster 2, patients receiving disease-modifying treatments had delayed progression to EDSS 6 (p=3×10-³), while no such benefit was observed in clusters 1 or 3. Cluster 2 patients also had earlier onset of symptoms, including dysphagia (p=0.02) and spasticity (p=8×10-⁴) in the NBB-MS cohort. Genetic clustering reveals clinically meaningful MS subtypes with distinct prognoses and treatment responses, highlighting its potential role in precision medicine for MS management.

Cerebral infarction is a frequent and serious complication of tuberculous meningitis (TBM), contributing substantially to morbidity and mortality. Moreover, studies on infarct patterns and associated factors/predictors remain limited in TBM. ACT-TBM trial (Aspirin or Clopidogrel Therapy in the Treatment of Tuberculous Meningitis) evaluated the efficacy and safety of adjunctive antiplatelet therapy (aspirin or clopidogrel) to standard antitubercular therapy in TBM for the occurrence of stroke or cerebral infarction. Here, we conducted a secondary analysis of the ACT-TBM trial to characterize the patterns, associated factors, and predictors of cerebral infarction in TBM. We utilized data of 237 patients from the ACT-TBM randomized controlled trial conducted at 2 tertiary centers in India (2019-2023). Serial magnetic resonance imaging and magnetic resonance angiography were performed at baseline, 1 month, and 3 months in the primary trial. Cerebral infarctions were categorized by size, vascular territory, and number. Multivariable logistic regression models were performed using variables with P<0.1 on univariable analysis and clinical relevance. Model estimates are reported as adjusted odds ratios (aORs) with 95% CIs. Of the 237 patients enrolled, 226 were included after excluding 11 with missing imaging or incomplete follow-up data. Among these, 84 (37%) had cerebral infarction. Median age of the entire cohort was 26 years (interquartile range, 20-36), and 134 (59.29%) were females. Multiple infarcts were observed in 66 (78.6%) patients, most frequently in the basal ganglia (n=61, 72.6%), subcortical white matter (n=44, 52.4%), and cortex (n=32, 38.1%). Arterial occlusion occurred in 52 (61.25%) patients with cerebral infarction versus 36 (25.55%) without (P<0.001). In multivariable adjusted models, Grade 3 TBM (aOR, 3.94 [95% CI, 1.19-13.08]; P=0.025), and arterial occlusion (aOR, 4.43 [95% CI, 2.19-8.96]; P<0.001) were associated with infarction. Among those with infarction, 27 (32.14%) patients (13.17% of the total cohort) developed new infarctions on follow-up. Modified antitubercular therapy (antitubercular therapy; aOR, 3.10 [95% CI, 1.18-8.09]; P=0.021) and arterial occlusion (aOR, 4.23 [95% CI, 1.40-12.75]; P=0.01) significantly predicted new infarctions. Presence of exudates was associated with arterial occlusion (aOR, 2.86 [95% CI, 1.08-7.56]; P=0.034). Cerebral infarction is common in TBM and associated with disease severity and arterial occlusion. Modified antitubercular therapy predicted new infarcts, while basal exudates were associated with vascular occlusion, highlighting the need for vigilant monitoring and optimized therapeutic strategies.

BackgroundThe conventional method of assessing radiotherapy outcome in brain metastases (BM) is based on monitoring tumor size alterations on serial magnetic resonance imaging (MRI). To accurately determine changes in tumor dimensions, targets require delineations on several volumetric images acquired before treatment and at multiple follow‐up scans after radiotherapy. However, manual tumor delineation on serial MRI is labor‐intensive, imposes a significant burden on the clinical workflow, and is prone to variability especially for smaller lesions.PurposeThis study proposes a novel multi‐step transformer‐based automated framework with a 3D neighborhood attention mechanism, specifically designed to enhance the segmentation precision for BM of various sizes on standard longitudinal MRI. This framework leverages the hierarchical encoding capabilities of transformer architecture to capture intricate tumor characteristics, with a particular focus on improving the delineation of small metastases (<1 cm), which are often overlooked by existing models.MethodsThe proposed framework was trained on the BraTS and BraTS‐METS datasets and evaluated on independent external data acquired from 212 patients (508 BM lesions) treated with stereotactic radiosurgery. The framework's performance was evaluated in segmenting tumors across various size categories, monitoring post‐treatment changes in tumor size on serial MRI, and automatically detecting local control/failure (LC/LF) and adverse radiation effect (ARE) following radiosurgery.ResultsThe framework achieved a dice score of 89.8 ± 3.4%, 92.0 ± 3.0%, and 93.1 ± 2.3% for tumors with a size of less than 1 cm, between 1 and 2 cm, and larger than 2 cm, respectively. It also demonstrated high performance in longitudinal monitoring of tumor size changes and in detecting LC/LF and ARE, achieving accuracies greater than 96% across different tumor size categories compared to the clinical outcome assessment. The results exhibited a substantial improvement over state‐of‐the‐art segmentation models, particularly for smaller lesions.ConclusionsThis study represents a step forward toward deploying AI‐driven decision support tools to the neuro‐oncology workflow, reducing the assessment burden on oncologists, and improving consistency in routine radiotherapy outcome assessments.

Interchangeable measure of pulmonary regurgitation in repaired tetralogy of Fallot: Comparison between serial cardiac CT and MRI.

Morphological changes of the preserved discoid lateral meniscus on serial magnetic resonance imaging following partial meniscectomy and repair: A comparison between immediate and 2-year postoperative findings.

Our objective was to establish a multicentre foetal-to-neonatal magnetic resonance (MR) neuroimaging programme for neonates undergoing surgery for complex congenital heart disease (CHD). We assessed structural and volumetric MRI findings at different timepoints in various types of CHD and evaluated neurodevelopmental outcomes at one year of age. Additionally, we analysed the feasibility, challenges and limitations of implementing this MR neuroimaging programme. In this prospective, multicentre observational study, we examined brain development and growth in infants with complex CHD requiring neonatal cardiac surgery. Brain MRI was performed at multiple timepoints: at the 32ndweek of gestation, after birth (both before and after stage I surgery), and before stage II surgery in single-ventricle CHD. We analysed and compared cardiac diagnoses, treatment approaches, structural and volumetric brain MRI findings and neurodevelopmental outcomes at one year of age (assessed using the Bayley III scale) with those of healthy controls. Between April 2020 and September 2023, 81 patients and 15 healthy controls underwent at least one MRI. Cardiac diagnoses were biventricular CHD (66.7%), single-ventricle CHD (25.9%) and borderline left ventricle CHD (7.4%). New structural cerebral lesions were found before stage I or after stage I including white matter injury in 3.8% and 8.7%, respectively, ischaemic cerebral lesions in 11.5 and 11.6%, intraventricular haemorrhages in 7.7% and 7.2%, and subdural haemorrhages in 33.6% and 26.1%. Total brain volume at 32.6 (interquartile range [IQR]: 31.3-33.3) gestational weeks was 228.9 ml (213.1-241.2) in biventricular CHD, 194.4 ml (165.3-223.6) in single-ventricle CHD and 196.4 ml (186.4-235.2) in normal healthy controls. After birth, at 6 days (3-16) of life total brain volume was 337.1 ml (310.3-350.2) in biventricular CHD, 331.6 ml (305.9-350.7) in single-ventricle CHD and 406.8 ml (389.9-438.7) in normal healthy controls. After stage I, at 26.5 days (18.3-40.8) total brain volume was 367.7 ml (341.8-385.5) in biventricular CHD, 353.6 ml (338.2-375.7) in single-ventricle CHD and 514.1 ml (482.9-554.6) at 116 days (94.5-118.5) in patients with single-ventricle CHD. At 12.1 months of age, neurodevelopmental performance determined by the Bayley III scale (mean ± SD [standard deviation]) was lower for patients with single-ventricle CHD (cognitive composite score [CCS]: 92.9 ± 13.1; language composite score [LCS]: 88.5 ± 12.0; motor composite score [MCS]: 85.6 ± 14.5) than in patients with biventricular CHD (CCS: 101.2 ± 11.1; LCS: 95.7 ± 13.1; MCS: 87.6 ± 18.0) or in healthy controls (CCS: 113.3 ± 5.6; LCS: 102.3 ± 7.9; MCS: 100.7 ± 8.2). Feasibility for performing cerebral MRI was limited due to maternal/patient safety reasons and further logistical infrastructural reasons. Structural cerebral lesions were found at various timepoints in both biventricular and single-ventricle CHD during foetal-to-neonatal serial cerebral MRI. Compared to healthy controls, total brain volume was reduced in patients with complex CHD, and neurodevelopmental outcomes at one year of age were mildly to moderately impaired. Several patient-related and infrastructural challenges limit the feasibility of a routine magnetic resonance neuroimaging programme, necessitating further efforts to optimise its implementation into routine clinical practice in the future. ClinicalTrials.govNCT04233775.

Morphological changes observed on serial magnetic resonance imaging of repaired medial meniscal horizontal cleavage tears.

BackgroundThe ASPIRE‐FTD study aims to evaluate the safety, tolerability and preliminary efficacy of AVB‐101 in patients with frontotemporal dementia due to progranulin mutations (FTD‐GRN). AVB‐101 uses an adeno‐associated virus 9 vector to deliver a functional copy of the GRN gene to thalamic neurons, which secrete and distribute progranulin (PGRN) throughout the brain. Direct intrathalamic delivery of AAV gene therapy has potential to achieve broad cortical biodistribution of PGRN, overcoming the challenges associated with the blood‐brain‐barrier and pial membrane, while using relatively low AAV doses versus intrathecal delivery. Here, we report preliminary safety from the first completed cohort.MethodThis ongoing Phase 1/2 open‐label, ascending dose study (NCT06064890) will evaluate up to three dose levels of AVB‐101 in the dose escalation part, and further subjects may be dosed in the expansion part to provide additional safety and efficacy data. All subjects will receive a one‐time, bilateral intrathalamic infusion of AVB‐101 under real‐time magnetic resonance imaging (MRI) guidance. The primary objective is to evaluate safety and tolerability of AVB‐101: safety measures include adverse events (AEs) (related or not to AVB‐101 and the administration procedure), change from baseline in MRI results and clinical/laboratory assessments. Neurofilament light (NfL) protein in plasma and cerebrospinal fluid (CSF) is also measured.ResultsAVB‐101 was well‐tolerated in all three patients at the dose level tested in this initial cohort. No clinically significant safety findings have been observed through the follow‐up period of up to 39, 26 and 12 weeks respectively for the three dosed subjects to date. Serial safety MRI demonstrated no significant hemorrhage, edema or inflammation.There have been no serious AEs reported to date and no AEs related to AVB‐101 or the neurosurgical procedure. Additionally, neither prophylactic nor reactive immunosuppression has been required for any subject.As expected, an early transient peak in serum and CSF NfL protein expression was observed after AVB‐101 administration, with trend to baseline thereafter.ConclusionPreliminary data from the ongoing ASPIRE‐FTD trial suggests a favorable safety profile for AVB‐101 and the administration procedure. Recruitment is ongoing for the subsequent escalated dose cohort.

Abstract Meningoencephalitis of unknown origin (MUO) is an immune-mediated central nervous system disorder in dogs in which magnetic resonance imaging (MRI) plays a key role in diagnosis and monitoring. This case report describes a five-year-old spayed female Chihuahua (3.9 kg) presented with acute right-sided weakness, anorexia, and vomiting. The initial MRI demonstrated multifocal T2/FLAIR hyperintense lesions in the left frontal lobe with suspected disruption of the blood–brain barrier, consistent with MUO. Immunosuppressive therapy with prednisolone (0.5 mg/kg twice daily, tapered to 0.15 mg/kg once daily) was administered in combination with imatinib (10 mg/kg once daily). Follow-up MRI after seven weeks revealed partial remission of lesions, restoration of blood–brain barrier integrity, and mild ventricular enlargement. At eleven months, chronic gliosis, progressive cerebral atrophy, and further ventricular dilation (39% vs. 29% at 7 weeks) were evident without new lesions. Clinical signs resolved within 25 days, but long-term therapy caused polyphagia, polydipsia, persistent alkaline phosphatase elevation, transient alanine aminotransferase increase, and episodes of hypertriglyceridemia. This case highlights the value of sequential MRI for documenting the transition from acute inflammation to partial remission and chronic structural change in MUO. Prednisolone-based immunosuppression combined with imatinib achieved sustained clinical improvement, while long-term monitoring was essential to detect progressive atrophy and treatment of related adverse effects.

BackgroundNeurological disorders, such as stroke and traumatic brain injury are the most significant global health challenges, leading to long-term physical and cognitive impairments. Cell transplantation therapy holds substantial promise for facilitating recovery, with numerous clinical trials currently underway. Intracerebral stem cell infusion offers the advantage of directly delivering a sufficient number of stem cells to the targeted area. Both our team and other researchers have observed a notable phenomenon following intracerebral stem cell therapy in clinical trials, wherein transient edema, as detected by Fluid Attenuated Inversion Recovery (FLAIR) magnetic resonance (MR) imaging, can be monitored between one and two weeks post-transplantation, with a subsequent resolution occurring approximately one month later. Notably, patient recovery appears to accelerate during the period of elevated FLAIR signals. However, the precise mechanisms underlying this distinctive phenomenon remain poorly understood. Therefore, this reverse translational research employs proteomics and histological analysis to investigate the mechanisms driving this phenomenon, thereby enhancing our understanding of stem cell therapy.MethodsBone marrow-derived mesenchymal stem cells (BMSCs) were isolated from Sprague-Dawley (SD) rats, with passage 3 cells utilized for subsequent experiments. A total of one million cells, suspended in 10 µL of phosphate-buffered saline, were intracerebrally transplanted into the striatum of SD rats. Serial magnetic resonance imaging (FLAIR) scans were performed up to three weeks post-transplantation. Brain tissues were collected from the pre-signal (1 week post-transplantation), signal (2 weeks post-transplantation), and post-signal (3 weeks post-transplantation) groups for proteomic analysis, network analysis, and immunofluorescence imaging.ResultsConsistent with clinical trials, transient FLAIR hyperintense signals were not detected until approximately two weeks post-intracranial stem cell therapy. These signals emerged around week two and diminished by week three. Proteomic analysis of brain specimens from the pre-signal and signal groups identified 231 differentially expressed proteins, which were primarily involved in vesicle-mediated transport, synaptic remodeling, and cellular communication. Glial fibrillary acidic protein (GFAP), Aquaporin-4 (AQP4), and Apolipoprotein E (APOE) were identified as key hub proteins. Immunofluorescence studies further confirmed that expression levels of GFAP, AQP4, and APOE increased around two weeks post-transplantation and significantly decreased by week three, coinciding with the resolution of the FLAIR signal.ConclusionsOur findings suggest that the transient FLAIR hyperintensity observed following intracerebral stem cell therapy is primarily attributed to transient glial cell activation, resulting in increased AQP4 expression and transient brain water influx. Additional mechanisms, including vesicle-mediated transport, secretion, synaptic activity, and lipid signaling, also contribute to the transient FLAIR hyperintensity signals and may play a role in the manifestation of clinical symptoms.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13287-025-04757-w.

Abstract BACKGROUND GBM AGILE (Glioblastoma Adaptive, Global, Innovative Learning Environment) is a multi-arm, international, seamless Phase 2/3 response adaptive randomization (RAR) platform trial designed to efficiently identify investigational therapies that improve overall survival and confirm efficacious therapies and biomarker signatures to support registration. GBM AGILE is a collaboration among academic investigators, patient organizations, and industry to support new drug applications for newly diagnosed and recurrent glioblastoma. METHODS The primary objective of GBM AGILE is to identify therapies that improve overall survival in patients with newly diagnosed or recurrent glioblastoma. Operating under a Master Protocol, GBM AGILE allows multiple drugs from different companies to be evaluated simultaneously and/or over time against a common control. Investigational therapies are added as information about promising drugs is identified, while other therapies are removed as they complete evaluation. RAR is used within subtypes of the disease to assign participants to investigational arms based on their performance. GBM AGILE has screened over 2300 patients and enrollment continues to be robust. In addition to the efficient evaluation of investigational arms, a goal of GBM AGILE is to expand knowledge of glioblastoma to support advancements in treatment using the data collected within the trial (learning environment). Over 7 million data points are currently available for inclusion in the development of a longitudinal model. Such a model may be able to inform randomization by providing earlier and continuous information regarding patient and arm performance. In addition, serial magnetic resonance imaging scans and biospecimens from baseline through patient progression are being collected for further analysis. An initial 500 baseline tissue samples are being characterized by genome sequencing and transcriptome analysis. NCT number: NCT03970447.

Abstract Grade 2 IDH mutant gliomas are known to undergo malignant transformation (MT). Early prediction of this transformation remains a significant clinical challenge. Radiomics, the extraction of high-dimensional imaging features, has emerged as a promising tool for non-invasive tumor characterization. Our study looked to implement quantitative radiomics analyses to identify textural information from clinical imaging that might enhance the prediction of MT in grade 2 IDH-mutant gliomas. We conducted a retrospective analysis of institutional (UCLA) and public (UCSF-PDGM) datasets with histologically confirmed IDH-mutant gliomas. Institutional dataset included patients underwent serial magnetic resonance imaging (MRI) and had pathologic clinical progression and/or transformation with at least one repeat biopsy/surgery. Radiomic features were extracted from T1-subtraction maps, T2-weighted images, and apparent diffusion coefficient (ADC) maps from diffusion MRI scans. The T2-hyperintense lesion was segmented, excluding necrosis, using NS-HGlio (Neosoma Inc, Groton, MA). UCLA patients were categorized based on the presence or absence of MT, defined as progression from WHO grade 2 to grade 3 or 4 by histology at repeat biopsy/surgery. Machine learning models, including random forest and support vector machines, were trained on 75% UCSF-PDGM dataset to classify grade 2 versus grade 3/4 tumors, validated on the remaining 25%. The model was used to generate a radiomics risk-score to predict MT in the UCLA dataset, evaluated using the ROC analysis. Model achieved AUC of 0.814 (CI: 0.73--0.90) on the UCSF training set (n = 77). On the UCSF test set (n = 26), sensitivity was 0.93, specificity 0.92, with AUC of 0.92 (CI: 0.80–1.00). Evaluation on the independent dataset of UCLA patients at the second surgical timepoint (n = 59) demonstrated a sensitivity of 0.69, specificity of 0.76, and AUC of 0.73 (CI: 0.61–0.84). Radiomics may enable non-invasive prediction of MT in IDH-mutant gliomas, outperforming conventional clinical models.

Abstract Brain metastases occur when cancer cells from a pre-existing tumor “break off” and spread to the brain via the bloodstream. Treatment often consists of surgical excision alongside radiation for a solitary metastasis, while radiation and/or chemotherapy are used for multiple brain metastases. Predicting the risk factors for patients developing this disease has been difficult to attain. In this study, we investigated the potential of perilesional cerebrospinal fluid (CSF) analysis as a biomarker for predicting the development and progression of intracranial metastatic disease. CSF analysis consisted of fluid sampling of the pre-resected perilesional subarachnoid CSF space to detect microscopic tumor cells. In this study, thirty-three patients (19 females and 14 males; median age: 65 years; range: 39-82 years) with brain metastases underwent craniotomy for local tumor resection. Patients with known leptomeningeal disease were excluded from this study. Primary cancer origins included breast cancer (n=9), lung cancer - subdivided into small cell lung (n=2) and non-small cell lung (n=7) - renal cell carcinoma (n=4), skin cancer (n=3), esophageal cancer (n-2), and gastroesophageal (n=1). Before tumor resection results demonstrated the presence of tumor cells (based on histology) in the local CSF and around subarachnoid space in ten patients. Additionally, for these patients, those diagnosed with breast (70%) or non-small cell lung cancer (20%) were more likely to have malignant cells present. Among breast cancer patients (n=9), 77.8% (n=7) were positive for malignant cells in pre-resection washing, followed by the progression of intracranial metastatic disease. Follow-up serial MR imaging did not find any patient with local recurrence at this time. With these results, perilesional CSF could serve as a novel biomarker for an early detection of distant CNS progression and influence the management of patients with brain metastasis. Further studies will be elucidating the genetic features of these tumor cells.

Acute Primary Anterior Cruciate Ligament Repair for Sherman Type I and II Tears Shows Significantly Improved Clinical Outcome and Ligamentous Maturation by Serial Magnetic Resonance Imaging Analysis.

BackgroundThe importance of the left ventricle after ST-segment elevation myocardial infarction (STEMI) has been well established; however, the role of left atrial (LA) dynamics in reverse left ventricular remodeling (R-LVR) remains unclear. This study aimed to assess structural and functional changes in the left heart by serial cardiovascular magnetic resonance (CMR) imaging, exploring the predictive value of the left atrium and left ventricle for R-LVR.MethodsA total of 105 patients with STEMI were retrospectively enrolled in the study, and data on their baseline clinical characteristics and CMR features at 4 days and 5 months after percutaneous coronary intervention (PCI) were collected. The CMR evaluation included the LA and left ventricular (LV) volumes, myocardial function, and infarct characteristics. The patients were categorized into two groups according to the presence of R-LVR, which was assessed by comparing the two CMR examinations; 47 patients were assigned to the R-LVR group, and 58 to the non-R-LVR group. Subsequently, the baseline clinical and CMR characteristics of these two groups were compared. The R-LVR predictors were identified by logistic regression. Three predictive models were built to explore the incremental value of the left heart function parameters for R-LVR prediction, using the Net Reclassification Index (NRI).ResultsAt first CMR, the R-LVR group had higher LV and LA volumes, and LV longitudinal displacement, as well as a lower myocardial injury value and LA reservoir strain rate (all P<0.05). At the second CMR, the R-LVR group had a lower LV volume, a smaller infarct mass, and greater left ventricular ejection fraction (LVEF) (all P<0.05). Notably, the left ventricular end-diastolic volume (LVEDV) [odds ratio (OR): 1.022, 95% confidence interval (CI): 1.007–1.037, P=0.005], infarct mass (OR: 0.946, 95% CI: 0.918–0.975, P<0.001), and LA reservoir strain rate (OR: 0.224, 95% CI: 0.055–0.905, P=0.036) were independent predictors of R-LVR. When LV longitudinal displacement and the LA reservoir strain rate were introduced into the model, the NRI was 44.10%.ConclusionsThis study assessed the predictive value of the LVEDV, infarct mass, and LA reservoir strain rate by CMR, and found that the combination of the LA reservoir strain rate and LV longitudinal displacement improved model prediction of R-LVR.

Apparent Diffusion Coefficient Magnetic Resonance Imaging as a Predictive Biomarker for Hypoxia, Treatment De-escalation, and Recurrence in Human Papillomavirus-Associated Oropharyngeal Cancer.

Myocardial infarction (MI) contributes to significant morbidity and mortality globally. Platelet derived growth factor-AB (PDGF-AB) is potentially a novel translational therapeutic for improving cardiac function post-MI, which we assess here using a 60 day porcine left anterior descending artery occlusion ischemia-reperfusion model. MI was induced in 10 female Landrace swine, with 5 controls, 5 receiving PDGF-AB treatment and 2 additional shams. PDGF-AB improved left ventricular ejection fraction 58 days after MI, without affecting overall infarct scar size, as shown using serial cardiac magnetic resonance imaging. Preserved infarct zone microvascular function and increased vessel maturity was also observed. Multi-omic analyses showed that PDGF-AB treatment altered the expression of proteins, metabolites, and lipids that are known to be involved in myocardial energetics and redox balance. Novel therapeutics such as PDGF-AB may lead to more sustained salvage of cardiac function by modulating the post-MI microvasculature, myocardium and extracellular matrix.

Serial MRI Measures Short-term Parenchymal Changes in Neonatal Bronchopulmonary Dysplasia.

PurposeCholedochal cyst is a rare, congenital dilation of the hepatobiliary tree. Due to the associated malignancy risk, complete resection is recommended. There remains a risk of metachronous cholangiocarcinoma despite resection necessitating lifelong surveillance. Choledochal cysts are increasingly prevalent with an incompletely understood connection to carcinogenesis. We sought to develop a mouse model to reliably mimic human disease process of choledochal cyst.MethodsExperimental transgenic mice were bred with a genotype of Pdx-Cre, TGFα, LSL-KRAS G12D Mu/Wt. Control C57 mice were used as a comparison. Experimental and control mice underwent serial abdominal magnetic resonance imaging (MRI) from weaning to sacrifice.ResultsAll experimental mice developed fusiform, extrahepatic common bile duct dilation mimicking a Type I choledochal cyst. Choledochal cyst was present on imaging modalities upon weaning. Maximum common bile duct (CBD) diameter by MRI demonstrated a significantly larger diameter in the experimental group compared to the control group at 10 weeks.ConclusionAll experimental mice with a genotype of Pdx-Cre, TGFα, LSL-KRAS Mu/Wt developed a phenotype consistent with congenital choledochal cyst. This transgenic mouse model mimics the oncogenic nature of choledochal cyst and could be used to further study disease pathophysiology and novel interventions.