Magnetic Resonance Imaging Results Research Articles

Early MRI Can Predict the Indication for Surgery in Brachial Plexus Birth Injury: Results of the NAPTIME Study.

Magnetic resonance imaging (MRI) has not been routinely used for infants with brachial plexus birth injury (BPBI); instead, the decision to operate is based on the trajectory of clinical recovery by 6 months of age. The aim of this study was to develop an MRI protocol that can be performed without sedation or contrast in order to identify infants who would benefit from surgery at an earlier age than the age at which that decision could be made clinically. This prospective multicenter NAPTIME (Non-Anesthetized Plexus Technique for Infant MRI Evaluation) study included infants aged 28 to 120 days with BPBI from 3 tertiary care centers. Subjects had nonsedated non-contrast rapid volumetric proton density MRI on 3-T scanners. Neuroradiologists at each site calculated the NAPTIME nerve root injury score for subjects at their site. Interrater reliability was performed on a subset of subjects. All of the subjects were evaluated with routine clinical examinations up to 6 months of age, by which time the treating surgeon determined whether to offer nerve surgery. Surgeons were blinded to the MRI results. The ability of the NAPTIME score to discriminate surgeon indication for surgery was evaluated using the receiver operating characteristic (ROC) curve, by estimating the area under the curve (AUC) across the range of NAPTIME scores. Sixty-five infants successfully completed the NAPTIME MRI; 18 (28%) ultimately met the clinical criteria for nerve surgery. The interrater reliability for the NAPTIME score was moderate at 0.703 (95% confidence interval [CI], 0.582 to 0.818). The median NAPTIME score for subjects who met the criteria for nerve surgery was 16.2 (interquartile range [IQR], 9.9 to 18.9), while the median score for those who did not was 7.0 (IQR, 5.0 to10.5). The NAPTIME score predicted meeting the criteria for surgery with an AUC of 0.812 (95% CI, 0.688 to 0.936). A score of >13 offered a specificity of 0.94 and a sensitivity of 0.61 for surgical indication. Non-contrast MRI without sedation is a useful tool in determining the severity of injury in BPBI. The NAPTIME score might distinguish which infants will meet the criteria for reconstructive nerve surgery earlier than when the decision can be made clinically. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Hemoglobin Decrements are Associated with Ischemic Brain Lesions and Poor Outcomes in Patients with Intracerebral Hemorrhage.

Acute ischemic lesions seen on brain magnetic resonance imaging (MRI) are associated with poor intracerebral hemorrhage (ICH) outcomes, but drivers for these lesions are unknown. Rapid hemoglobin decrements occur in the initial days after ICH and may impair brain oxygen delivery. We investigated whether acute hemoglobin decrements after ICH are associated with MRI ischemic lesions and poor long-term ICH outcomes. Consecutive patients with acute spontaneous ICH enrolled into a single-center prospective cohort study were assessed. Change in hemoglobin levels from admission to brain MRI was defined as the exposure variable. The presence of MRI ischemic lesions on diffusion-weighted imaging was the primary radiographic outcome. Poor 6-month modified Rankin Scale score (4-6) was assessed as our clinical outcome. Separate regression models assessed relationships between exposure and outcomes adjusting for relevant confounders. These relationships were also assessed in a separate prospective single-center cohort of patients with ICH receiving minimally invasive hematoma evacuation. Of 190 patients analyzed in our primary cohort, the mean age was 66.7years, the baseline hemoglobin level was 13.4g/dL, and 32% had MRI ischemic lesions. Greater hemoglobin decrements were associated with MRI ischemic lesions (adjusted odds ratio [OR] 0.77 for every 1g/dL change, 95% confidence interval [CI] 0.60-0.99) and with poor 6-month outcomes (adjusted OR 0.73, 95% CI 0.55-0.98) after adjusting for demographics, ICH and medical disease severity, and antithrombotic use. In our separate cohort of 172 surgical patients with ICH, greater hemoglobin concentration decrements similarly associated with MRI ischemic lesions (adjusted OR 0.74, 95% CI 0.56-0.97) and poor 6-month outcomes (adjusted OR 0.69, 95% CI 0.48-0.98). Greater hemoglobin decrements after acute ICH are associated with ischemic lesions on brain MRI and poor long-term outcomes. Further work is required to clarify drivers for these relationships and whether anemia treatment and prevention can be used to improve ICH outcomes.

Diagnostic Value of Serum miR-499a-5p in Chinese Children with Autism Spectrum Disorders.

The purpose of this study was to investigate the expression of miR-499a-5p in children with autism spectrum disorders (ASD) and its value in early diagnosis of ASD. This is a retrospective case-control study that included 40 children with ASD as a case group and 43 healthy children as a control group. Magnetic resonance imaging (MRI) was performed on all subjects, and the children were scored with childhood autism rating scale (CARS) and autism behavior checklist (ABC). The expression of miR-499a-5p in serum was detected by RT-qPCR, and the diagnostic value of miR-499a-5p in ASD was evaluated by ROC curve. Pearson correlation coefficient was used to evaluate the correlation between miR-499a-5p levels and scores. Compared with healthy children, the expression level of serum miR-499a-5p was significantly reduced in children with ASD. ROC curve showed that miR-499a-5p is of high diagnostic value for ASD. The results of MRI suggested that the volume of the amygdala in ASD children was significantly larger than that in healthy children, while the volume of the caudate nucleus was significantly reduced. Correlation results showed that the scores of CARS and ABC in the ASD group were significantly negatively correlated with the levels of miR-499a-5p. In the ASD group, the volume of the amygdala was negatively correlated with the level of miR-499a-5p, while the volume of the caudate nucleus was positively correlated with the level of miR-499a-5p. The decreased expression of miR-499a-5p in the serum of children with ASD was significantly related to the changes in brain volume of children with ASD, and the miRNA showed good diagnostic accuracy in children with ASD.

DEPDC5 mutations in familial epilepsy syndrome: genetic insights and therapeutic approaches

Background. DEPDC5 (disheveled, Egl-10 and pleckstrin domain-containing protein 5) familial epilepsy syndrome is a group of epilepsy disorders caused by mutations in DEPDC5 gene, which is a part of the gap activity towards rag 1 (GATOR1) complex involved in regulating the mechanism target of rapamycin (mTOR) pathway. These mutations lead to hyperactivation of the mTOR pathway, disrupting the shaping of neurons and resulting in increased excitatory transmission and the development of epilepsy. The incidence and prevalence of DEPDC5 familial epilepsy syndrome are not well established, but studies suggest it may account for up to 10% of familial focal epilepsy cases. Genetic testing, electroencephalography (EEG), and brain magnetic resonance imaging (MRI) are important in diagnosing the disorder, although normal MRI results are common.Objective: to explain the rare sporadic mutation in DEPDC5 gene with p.R389H, a variant of unknown significance.Case report. A 6-year-old South-Asian girl was born at 34-weeks from non-consanguineous marriage without any prenatal events. She had hyperbilirubinemia by week-1, which was successfully treated with phototherapy. Her initial seizure occurred when she was three months old, just 2 days after the fever from the vaccination had subsided. It was considered a simple-febrile seizure and no treatment was given. At 3.5-months, she started having recurrent seizures. Workup including MRI/ infectious/metabolic panel was non-conclusive. EEG during the initial presentation showed epileptiform activity from the left temporal region. Despite being on multiple anti-epileptic drugs, the child was diagnosed with refractory epilepsy. Subsequently, EEG at 2.5-years showed inter-ictal bi-hemispheric epileptiform activity. EEG at 5-years showed inter-ictal spikes and wave discharges from bilateral fronto-temporal region with secondary generalization. By 3-years, MRI showed mildly deformed corpus callosum with inadequate thickening of splenium. DNA analysis confirmed heterozygous missense mutation in exon 16 of DEPDC5 gene, without chromosomal abnormalities. Mother was heterozygous for the same mutation but no mutations in the father was found. The child has grossly delayed milestones. Corrected age is approximately 1-year for fine motor and language, 1.5-years for gross motor, 2.5-years for cognition, social skills. She had developed autistic features as well with significant impaired auditory/visual processing. She had hypotonia (Right>Left), wide-based gait, and extrapyramidal movements.Conclusion. DEPDC5 gene mutation results in amino acid substitution of Histidine for Arginine at codon 389. This mutation has shown to be inherited in familial pattern. This R389H variant is not present in the 1000 genomes database and is predicted to be benign. However, It rather appears to be a sporadic mutation, which is a very rarely observed phenomena. Such patients may respond well to mTOR inhibitors such as rapamycin, making prompt diagnosis and treatment crucial.

Clinical and magnetic resonance imaging outcome after proximal hamstring tendon repair at mean 3 years follow-up

PurposeThe purpose of this study was to assess clinical and radiological outcome in patients after proximal hamstring tendon repair. We hypothesized that there is a significant correlation among subjective clinical outcome and interlimb asymmetries in muscle strength, fatty infiltration, and hamstring volume.MethodsThis retrospective monocentric case series included patients with surgical repair after proximal hamstring tendon rupture. Clinical outcome was assessed utilizing: Healthy Days Core Module (CDC HRQOL-4), numeric pain rating scale (NRS), modified Harris Hip Score (mHHS), Tegner Activity Scale (TAS), return to pre-injury activity level (RTPA), and patient satisfaction score. Postoperative hamstring strength was measured using a handheld dynamometer and radiological outcome was determined by postoperative magnetic resonance imaging (MRI).ResultsTwenty-seven patients with a mean age of 51.2 (± 12.6) years were available for follow-up at a mean of 41.11 (± 18.4) months. Patients state a mean of 10.6 (± 11.5) days in the unhealthy days (UHD) index and 88.9% show “good health” in the simple summary score (SSS). Mean subjective outcome scores were as follows: NRS 1.1 (± 2.4), mHHS 90.3 (± 14.8) and TAS 5.7 (± 2.2). A total of 59.3% RTPA and 88.9% state to be somewhat or very satisfied with their surgery. Mean interlimb strength ratio was 0.88 (± 0.21). MRI demonstrated a fully restored muscle–tendon unit, significantly greater fatty infiltration in the injured hamstrings (p = 0.009, d = 0.558), and a mean interlimb hamstring volume ratio of 0.94 (± 0.11). With respect to the 10% benchmark, patients had no significant asymmetries in muscle strength (p = 0.677, d = 0.084) or hamstring volume (p = 0.102, d = − 0.34). Correlation analysis revealed moderate correlation among asymmetries in strength and volume (p = 0.073, r = 0.373). In patients with the operated side inferior to the healthy side (n = 15), there was strong correlation among asymmetries in strength and volume (p = 0.002, r = 0.725). Statistically significant correlation was found between interlimb muscle volume atrophy and increase in fatty infiltration (p = 0.015, r = 0.481).ConclusionProximal hamstring repair results in good clinical outcome with satisfactory recovery of hamstring strength and volume. Interlimb asymmetries, in terms of muscle strength, fatty infiltration, and hamstring volume do not correlate with clinical outcome.Study TypeRetrospective cohort study; Level of evidence, 3.

Concordance of Prenatal Ultrasonography and Magnetic Resonance Imaging in the Classification of Corpus Callosum Dysplasia

Background: Prenatal ultrasound has always been difficult to classify fetal corpus callosum abnormalities. This paper aims to evaluate the added value of fetal magnetic resonance imaging (MRI) to ultrasound in detecting fetal corpus callosum anomalies and the consistency of the classification of prenatal ultrasound and magnetic resonance imaging for corpus callosum anomalies. Methods: A retrospective analysis was performed of fetuses with abnormal cavum septi pellucidi who had ultrasonography and MRI in utero in Sichuan Maternal and Child Health Hospital and Wenjiang District Maternal in China and Child Health Hospital from January 2018 to December 2023. Fetal corpus callosum anomalies are classified according to the severity of the findings. The classification results of MRI were used as the diagnostic criteria. The findings detected on ultrasound (US) were compared to those detected on MRI. and the receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specificity of prenatal ultrasound in diagnosing corpus callosum anomalies. The Kappa test was used to analyze the consistency of prenatal ultrasound and MRI in the classification of corpus callosum anomalies. Results: Of the 203 cases of fetuses with abnormal cavum septi pellucidi, 143 cases (70.4%) were normal, 34 cases (16.7%) had complete agenesis of the corpus callosum, and 18 cases (8.9%) had partial agenesis of the corpus callosum. Eight cases (3.9%) had dysplasia of the corpus callosum. The area under the ROC curve of prenatal ultrasound for the diagnosis of corpus callosum anomalies was 0.840 (95% confidence interval (CI) 0.782–0.888), the sensitivity was 75.00%, and the specificity was 93.01%, The positive likelihood ratio was 10.7 and the negative likelihood ratio was 0.3. Prenatal ultrasonography and MRI had moderate concordance in the classification of corpus callosum anomalies (Kappa = 0.673, p < 0.001). The concordance was good in diagnosing complete agenesis of the corpus callosum (Kappa = 0.862, p < 0.001), while the concordance was moderate in diagnosing partial agenesis of the corpus callosum (Kappa = 0.643, p < 0.001). Conclusions: Prenatal ultrasonography is accurate and effective in the diagnosis of corpus callosum anomalies. Magnetic resonance imaging can provide more information in the classification of corpus callosum anomalies and the diagnosis of neurologic complications. The MRI should be combined with ultrasonographic transverse, midsagittal, and coronal views to evaluate the classification of corpus callosum anomalies.

Clinical and genetic features of childhood-onset congenital combined pituitary hormone deficiency: a retrospective, single-center cohort study.

To investigate the clinical characteristics and genetic features of childhood-onset congenital combined pituitary hormone deficiency (cCPHD) in Korean patients. We retrospectively analyzed 444 patients diagnosed with childhood-onset CPHD at a tertiary center between 1994 and 2021. After excluding acquired case, 43 patients with cCPHD were enrolled. Anthropometric measurements, hormone evaluations, brain magnetic resonance imaging (MRI), extrapituitary phenotypes, and adult outcomes were analyzed. Genetic analyses were performed on 26 patients using a targeted gene panel or whole exome sequencing. Mean age at diagnosis was 3.2 years, and 41.9% were diagnosed at less than 1 year old. Short stature was the most frequent (37.2%) initial presentation, and mean height z-score was -2.4. More than half (n=23, 53.5%) of patients had neonatal features suggestive of hypopituitarism; however, only 15 (65.2%) were diagnosed in infancy. Growth hormone deficiency (GHD) was prevalent in 42 (97.7%), and 33 (76.7%) had 3 or more hormone deficiencies. Extrapituitary phenotypes were identified in 31 (72.1%). Brain MRI abnormalities correlated with a higher number of hormone deficiencies (P for trend 0.049) and were present in 33 patients (80.5%). Adult GHD was diagnosed in all 17 investigated patients, and metabolic disturbances were noted in 10 (58.9%). Pathogenic variants in POU1F1, GLI2, HESX1, TBC1D32, and ROBO1 were found in 5 (19.2%). Considering the high proportion of neonatal presentations, identification of the early neonatal features of hypopituitarism to manage pituitary and extrapituitary phenotypes is critical. The genetic etiology of cCPHD warrants further exploration.

Ex vivo imaging of subacute myocardial infarction with ultra-short echo time 3D quantitative T1- and T1ρ -mapping magnetic resonance imaging in mice.

The aim of this study was to develop an ultra-short echo time 3D magnetic resonance imaging (MRI) method for imaging subacute myocardial infarction (MI) quantitatively and in an accelerated way. Here, we present novel 3D T1- and T1ρ -weighted Multi-Band SWeep Imaging with Fourier Transform and Compressed Sensing (MB-SWIFT-CS) imaging of subacute MI in mice hearts ex vivo. Relaxation time-weighted and under-sampled 3D MB-SWIFT-CS MRI were tested with manganese chloride (MnCl2) phantom and mice MI model. MI was induced in C57BL mice, and the hearts were collected 7 days after MI and then fixated. The hearts were imaged with T1 and adiabatic T1ρ relaxation time-weighted 3D MB-SWIFT-CS MRI, and the contrast-weighted image series were estimated with a locally low-rank regularized subspace constrained reconstruction. The quantitative parameter maps, T1 and T1ρ , were then obtained by performing non-linear least squares signal fitting on the image estimates. For comparison, the hearts were also imaged using 2D fast spin echo-based T2 and T1ρ mapping methods. The relaxation rates varied linearly with the MnCl2 concentration, and the T1 and T1ρ relaxation time values were elevated in the damaged areas. The ischaemic areas could be observed visually in the 3D T1, 3D T1ρ , and 2D MRI maps. The scar tissue formation in the anterior wall of the left ventricle and inflammation in the septum were confirmed by histology, which is in line with the results of MRI. MI with early fibrosis, increased inflammatory activity, and interstitial oedema were determined simultaneously with T1 and T1ρ relaxation time constants within the myocardium by using the 3D MB-SWIFT-CS method, allowing quantitative isotropic 3D assessment of the entire myocardium.

The value of signal intensity ratios of orbital tissue to white matter of orbital MRI in evaluating graves' orbitopathy.

PURPOSE: To investigate the signal intensity ratio (SIR) of orbital tissue to white matter in orbital magnetic resonance imaging (MRI) for assessing graves' orbitopathy (GO). This study enrolled a total of 42 patients (79 eyes) with GO as the GO group, 10 patients (20 eyes) diagnosed with graves' disease (GD) without orbitopathy during the same period as the GD group, and 23 normal individuals with negative MRI results and no thyroid or eye diseases as the healthy control (HC) group. The signal intensity of the lacrimal gland (LG), extraocular muscle (EOM), ipsilateral temporal muscle (TM), ramus mandibulae, and white matter (WM) on MRI images was measured. Patients in the GO group were categorized into active and inactive GO subgroups. The SIRs in the GO, GD, and HC groups showed significant differences. SIR-LG in relation to WM and SIR-EOMs in the GO group were significantly higher than those in the GD and HC groups. The SIRs in the active GO group were higher than those in the inactive GO group with significant differences, except for SIR-LG/TM. SIR-EOM/WM demonstrated higher accuracy than other SIRs in identifying GO activity. The area under the curve for SIR-EOM/WM was 0.81 (95% CI 0.71-0.91), with a sensitivity of 69.6%, specificity of 87.9%, and a cut-off value of 1.50. SIR-LG/WM and SIR-EOMs are objective indicators for discriminating between GO and the other two groups. Furthermore, SIR-EOM/WM may serve as a simpler quantitative MRI biomarker for identifying GO activity and are worthy of clinical generalization.

Agenesis of the corpus callosum combined with cerebral abnormalities: Clinical and diagnostic features

Background. Agenesis of the corpus callosum (ACC) is the total or partial absence of CC, one of the most common congenital brain malformations, with an incidence rate of 1.4 cases per 10,000 live births. Aim. To describe the clinical and diagnostic features of 4 patients with ACC. Materials and methods. Four patients with ACC aged 11, 12, 13, and 50 years were managed, of whom 3 were males, and 1 was a 13-year-old girl. All patients underwent a neurological examination, which assessed cognitive and mental disorders and electroencephalography. Patients underwent magnetic resonance imaging (MRI) in standard modes using a magnetic resonance imaging scanner with a magnetic field intensity of 1.5 T to detect damage to the brain's anatomical structure. Results. The disease was asymptomatic in 2 patients (a 50-year-old man and a 12-year-old boy). In the other 2 cases, there was an apparent neurological and cognitive deficit. The boy's parents and grandparents died of chronic alcoholism at the age of 11. During a neurological examination, he showed signs of damage to the pyramidal tract, as well as pronounced cognitive impairment with profound mental retardation, including delayed psycho-speech development. The 13-year-old girl suffers from severe mental retardation with speech impairment. In both cases, ACC was associated with epilepsy with a seizure frequency ranging from 6 times a year in the girl and up to 15 times a month in the boy. The gross neurological and cognitive deficits cause social difficulties since such patients need rehabilitation and ongoing care. In all cases, the diagnosis of ACC is based on the results of brain MRI, which is the method of choice. MRI enables assessment of the CC anatomical structure and the presence of other brain abnormalities. Complete agenesis was established in 3 cases, including a girl, and in one patient – a 12-year-old boy – partial agenesis with intact splenium was detected. In all patients, agenesis was combined with brain congenital malformations, namely with the absence of the septum pellucidum, interhemispheric and porencephalic cyst, basilar invagination, and venous malformation of the frontal lobe. Conclusion. ACC is a rare congenital brain malformation. According to the data, agenesis is more common in males. Complete ACC was diagnosed in 3 patients and partial ACC in 1. Risk factors include maternal alcohol consumption during pregnancy. The clinical presentation is diverse: from an asymptomatic course to severe cognitive impairment with severe and profound mental retardation, epilepsy, and autistic disorders with neurological deficits, including damage to the pyramidal tract. The primary diagnostic method is MRI, which detects anatomical changes in CC and other brain structures.

Oncological Safety of MRI-Informed Biopsy Decision-Making in Men With Suspected Prostate Cancer

The magnetic resonance imaging (MRI) pathway for diagnosing clinically significant prostate cancer (csPCa; defined as International Society of Urological Pathology grade group ≥2) uses multiparametric MRI (mpMRI) for prostate biopsy (PB) decision-making. However, the intermediate impact on patient outcomes in men with negative MRI results avoiding PB and men with positive MRI results without PCa remains unknown. To assess the feasibility and safety of a community-based MRI diagnostic strategy in men with suspected PCa using 3-year active monitoring. This multisite, longitudinal cohort trial took place across 54 community-based urology practices and 2 radiology imaging centers at a referral academic institution in Berlin, Germany. Eligible participants aged 18 to 75 years with clinically suspected PCa were enrolled between September 2016 and December 2017 and monitored for 3 years. Final analysis was reported on December 23, 2023. Participants underwent 3-T mpMRI. Men with findings suspected to be PCa were recommended for targeted PB (diagnostic phase). Men with negative mpMRI results or positive mpMRI results with benign findings at PB were systematically monitored for 3 years (monitoring phase). Clinical visits were recommended every 6 months. The total proportion of men avoiding PB and those with csPCa. A total of 593 men (median [IQR] age, 64 [58-70] years) underwent mpMRI, with 286 (48%) having negative MRI results, 261 (44%) avoiding PB initially, and 242 (41%) avoiding PB over 3 years. csPCa was detected in 161 (27%) men after immediate PB, increasing to 172 (29%) men after 3 years. Seven men with negative MRI results were diagnosed with PCa by immediate PB (including 4 cases of csPCa), while 279 entered monitoring. Three-year monitoring was completed by 233 (84%) men, with 7 diagnoses of csPCa. Of 307 men with positive MRI results, 58 (19%) showed no PCa after immediate PB, of which 41 (71%) completed monitoring and 4 (7%) were diagnosed with csPCa. In this cohort study, men with negative mpMRI results avoiding biopsy were not at elevated risk of csPCa. The study confirms the oncological safety of the prebiopsy MRI strategy of avoiding an immediate PB after negative MRI results when a programmatic safety net is in place.

An Overview of Anesthetic Procedures for Ferret (Mustela putorius furo) Preclinical Brain MRI: A Call for Standardization

AbstractNeuroscience research has been increasingly active during the last 2 decades, largely driven by the high prevalence and increasing burden of neurologic disorders. While rodents are essential models for biomedical research of neurologic disorders, they lack similar brain anatomy and protein expression profiles to humans, thus limiting their translational value as models of traumatic brain injury, stroke, Alzheimer’s disease, and Parkinson’s disease. The use of ferrets as a model species in neuroscience has been increasing due to their neuroanatomical similarities with humans, including a gyrencephalic brain and larger white matter-to-gray matter ratio. Compared with nonhuman primates, sheep, and swine, ferrets also have the advantages of reduced size, lower housing costs, and lower phylogenetic order. These, among other advantages, make ferrets a promising species to bridge research gaps and complement traditional rodent studies. Although modern neuroscience research in ferrets relies heavily on advanced imaging techniques such as magnetic resonance imaging (MRI), most of the preclinical MRI installations are not designed or optimized for use with ferrets. In this paper we discuss the intricacies and limitations that need to be considered when performing ferret MRI procedures. Reviews of ferret biologic peculiarities, anesthetic protocols, management of complications, and the impact of these factors on MRI outcomes are presented. Standardizing anesthesia protocols for the conduct of MRI in ferrets will aid in better physiologic monitoring as well as imaging outcomes that ultimately benefit the science being conducted.

Blood‐based Proteomic Profiling for the Progression of Cognitive Decline, Neuropsychiatric Symptomatology, and Neuroimaging Outcomes within an Asian Memory Clinic Cohort

AbstractBackgroundThe prognostic performance of plasma proteomics for longitudinal changes in (i)cognition (ii)neuropsychiatric symptomatology and (iii)neuroimaging outcomes within South East Asia, where prevalence of cerebrovascular disease is high, remains un‐investigated.MethodsA prospective cohort of Singaporean memory clinic attendees was followed‐up for 4 years. Annual neurocognitive and neuropsychiatric assessments were performed alongside 2‐yearly brain magnetic resonance imaging (MRI) scans. Incident cognitive decline was defined as a Clinical Dementia Rating Scale Sum‐of‐Boxes (CDR‐SB) ≥3 increment from baseline. Significant neuropsychiatric symptomatology progression was defined by a Neuropsychiatric Inventory score increment of ≥4 from baseline.Neuroimaging outcomes evaluated included (i)rates of progression of cerebral small vessel disease (white matter hyperintensity volume) and (ii)hippocampal atrophy on 2‐yearly MRI scans.1536 plasma proteins (encapsulating all major biological pathways including neurological, immune‐oncological, cardiovascular and inflammatory pathways) were profiled at baseline using the Olink Explore 1536 platform. Their associations with cognitive, neuropsychiatric and MRI outcomes were subsequently evaluated in multivariable regression models, with correction for false‐discovery rate.ResultsOf 528 subjects (mean age 72.83±7.81years, 43.8% male, 57.9% cerebrovascular disease, 22.4% NCI, 40.3% CIND, 37.3% dementia), the incidence of cognitive decline was 31.6% (167/528). Among 245 proteins significantly associated with cognitive decline, GFAP and NEFL were the most powerfully prognostic (Fig. 1).The incidence of significant progression of neuropsychiatric symptomatology was 55.68% (294/528). Among 310 proteins significantly associated with the progression of neuropsychiatric symptoms, NEFL and DCBLD2 were the most prognostic (Fig. 1).NEFL and TNFRSF11B were the most significantly dysregulated proteins for cerebral small vessel disease progression, while GFAP and NEFL significantly associated with rate of hippocampal atrophy. These top proteins also significantly associated with the rates of domain‐specific decline in 4 or more cognitive domains assessed over 4 years (Fig. 2).The top two gene ontology biological pathways identified from all data on significantly dysregulated proteins, were (i)cell adhesion and (ii)signal transduction, in both clinical entities (Fig. 3).ConclusionOur findings, upon interrogation of a biobank from a well‐annotated cohort, identifies late‐stage protein biomarkers and biological pathways for a suite of longitudinal cognitive, neuropsychiatric and neuroimaging outcomes. These biomarkers warrant further validation and mechanistic elucidation as potential therapeutic targets.

Optimization of Extended Pelvic Lymph Node Dissection Side for Prostate Cancer.

This study aimed to show the association between tumor location and laterality of positive lymph nodes by evaluating biopsy and magnetic resonance imaging (MRI) findings, and to optimize the extended pelvic lymph node dissection (ePLND) side for prostate cancer. The study enrolled patients who underwent robot-assisted radical prostatectomy with ePLND. Tumor locations were determined according to International Society of Urological Pathology grade group 4/5 in biopsies and Prostate Imaging-Reporting and Data System category 4/5 in MRI results. The concordance of tumor location lobe and positive lymph node side with the performance of tumor location-guided ePLND for positive lymph node detection was evaluated. For 301 patients who underwent ePLND at Kyushu University Hospital, tumor locations determined by biopsy and MRI findings showed no lesion in 8 (2.7%) patients, unilateral lobe in 223 (74.1%) patients, and bilateral lobe in 70 (23.3%) patients. The accuracies for detection of any and all positive lymph nodes by tumor location-guided unilateral ePLND were 99.6% and 97.3%, respectively. Among the patients at St. Luke's International Hospital, the accuracies for detection of any and all positive lymph nodes by tumor location-guided unilateral ePLND were estimated to be 99.0% and 97.3%, respectively. This study proposed tumor location-guided ePLND according to biopsy and MRI findings. This novel strategy is expected to reduce the burden of bilateral ePLND at the cost of acceptable risk of failing to detect positive lymph nodes.

Prevalence and timing of prenatal ultrasound findings incytomegalovirus-infected pregnancies.

To investigate the prevalence and timing of prenatal neurosonographic abnormalities after primary cytomegalovirus seroconversion by the first trimester of pregnancy. The additional value of magnetic resonance imaging (MRI) and the correlation between cytomegalovirus viral load in amniotic fluid and adverse neonatal outcomes were evaluated. A retrospective study between 2006 and 2022 examined data from 440 women with amniocentesis for periconceptional and first-trimester cytomegalovirus seroconversion. Cases with positive amniocentesis and subsequent follow-up were included. Prenatal neurosonography, MRI, and clinical outcomes were analyzed. Out of 190 women included, 37% (n = 70) presented with a normal neurosonography. Patients exhibiting abnormal neurosonography findings showed higher viral loads in amniotic fluid compared to those with a normal neurosonography (p = 0.002). In 26% (n = 49) the first abnormal ultrasound sign was already picked up at amniocentesis, and the most common ones were echogenic bowels (49%) and periventricular echogenicity (43%). With increasing gestational age, the likelihood of a new abnormal neurosonography finding decreases. MRI discovered additional abnormalities in 14% (n = 10). The results highlight the importance of combining diagnostic modalities, from amniocentesis to biweekly ultrasound monitoring and subsequent MRI evaluation, to capture the chronological progression and subsequent outcome of congenital cytomegalovirus.

Plasma Proteomic Determinants of Small Vessel Disease of the Brain: the Multi‐Ethnic Study of Atherosclerosis

AbstractBackgroundThe identification of novel blood‐based biomarkers of small vessel disease of the brain (SVD) may improve pathophysiologic understanding and inform the development of new therapeutic strategies for prevention. We evaluated plasma proteomic associations of white matter fractional anisotropy (WMFA), white matter hyperintensity (WMH) volume, enlarged perivascular space (ePVS) volume, and the presence of microbleeds (MB) on brain magnetic resonance imaging (MRI) in the population‐based Multi‐Ethnic Study of Atherosclerosis (MESA).MethodsEligible MESA participants had 2941 plasma proteins measured from stored blood samples (collected in 2016‐2018) using the antibody‐based Olink proteomics platform, and completed brain MRI scans in 2018‐2019. Participants with quality control exclusion of protein measurements, missing covariate data, and poor quality or missing MRI outcome variables were excluded. The cross‐sectional association between the abundance of each plasma protein (normalized protein expression – a relative protein quantification unit measured on a log2 scale) was modeled separately with WMFA, WMH volume, total ePVS volume, and the presence of MBs using multivariable linear or modified Poisson regression, adjusting for demographic variables, estimated glomerular filtration rate (eGFR), and SVD risk factors. The Benjamini‐Hochberg procedure was used to control the false discovery rate (FDR) <0.05 to account for multiple hypothesis testing. For proteins independently associated with the SVD markers on MRI, penalized regression with least absolute shrinkage and selection operator (LASSO) was used to create a parsimonious proteomic model.ResultsEligible participants (total N=709) had a mean age of 73 years, 53% were women, 25% were Black, 17% were Chinese, 19% were Hispanic or Latino, and 39% were White (Table 1). After adjustment for demographics, eGFR, and SVD risk factors, 769 plasma proteins were associated with WMFA (FDR <0.05) (Figure). LASSO regression identified a 37‐protein model predictive of WMFA (Table 2). We did not find plasma proteins to be independently associated with WMH volume, ePVS volume, or the presence of MBs.ConclusionMultiple circulating proteins – implicated in central nervous system myelination, lipid metabolism, angiogenesis, coagulation, cellular adhesion and migration, appetite regulation, energy homeostasis, systemic inflammation, and immune regulation – were independently associated with WMFA in a multi‐ethnic cohort of older adults.

OVERTURE Phase 2 MRI Analysis Demonstrates Reduced Corpus Callosum Atrophy in Alzheimer's Disease

AbstractBackgroundRecent research by Da et al. (2023) has demonstrated that non‐invasive gamma sensory stimulation can reduce brain white matter atrophy and myelin content loss. The impact on the Corpus Callosum (CC), the brain's largest commissural white matter tract essential for hemispheric connectivity, remains unexplored. Diffusion Tensor Imaging (DTI) studies (Delvenne et al. 2023), have identified variations and alterations in the CC's tract bundles in Alzheimer's disease (AD). We conducted an analysis of CC changes in patients along the Alzheimer’s continuum targeting both the overall and regional structural alterations.MethodIn this study, we used neuroimaging data from the OVERTURE clinical trial (NCT03556280). Participants were randomized 2:1 (Active: Sham) to receive daily, 1‐hour, audio and visual stimulation at gamma frequency or sham stimulation for 6 months. Magnetic Resonance Imaging (MRI) assessments were performed at baseline, month 3, and month 6. T1w MRI images were processed using the Yuki module within the Automated Registration Toolbox (ART) (Ardekani et al., 2014) with CC segmentation in the midsagittal plane (MSP) and its five subregions (Hampel et al., 1998). The analysis was conducted on participants with valid data for the total MSP CC and its subregions (N=50). Using Bayesian linear mixed‐effects modeling, we examined the changes in the area of the total MSP CC and its subregions.ResultThe active group demonstrated preservation of the total CC area and its subregions after six months of treatment. Differences in percentage changes between active and sham groups were: Total CC area (2.28±0.87%, p<.02), genu/rostrum (2.36±0.90%, p<.02), anterior‐body (2.64±1.26%, p<.04), mid‐body (2.79±1.18%, p<.03), posterior‐body (2.87±1.41%, p<.05) and splenium (1.58±0.73%, p<.04). Significant differences between the two groups were also observed in total CC area, genu/rostrum, and splenium at month 3.ConclusionOVERTURE Phase 2 MRI outcomes demonstrate that six months of non‐invasive gamma sensory stimulation may reduce the progression of CC atrophy in individuals with mild‐moderate AD, potentially preserving the integrity of interhemispheric communication. We are currently conducting a phase 3 clinical trial titled HOPE (NCT05637801) to evaluate the efficacy and safety of Cognito’s medical device.

EVALUATION OF THE RELATIONSHIP BETWEEN IRON LOAD, AGE, AND CARDIAC FUNCTION IN CHILDREN AND YOUNG ADULTS WITH THALASSEMIA MAJOR: A PULSED-WAVE DOPPLER AND TISSUE DOPPLER IMAGING STUDY

Objective: To determine the structural and functional cardiac differences in children and young adults with thalassemia major (TM) compared to healthy subjects using pulsed-wave Doppler and tissue Doppler imaging methods and determine the relationship between iron overload and these differences. Materials and Methods: We analyzed the data of pediatric and young adult TM patients (n = 44) aged 4–22 years and an age- and gender-matched control group (n = 40) in our hospital data system between Oct.01.2023 and Oct.01.2024. Height, weight, body mass index (BMI), systolic–diastolic blood pressure measurements, complete blood count, ferritin, cardiac T2* magnetic resonance imaging (MRI) values, and echocardiography results were recorded. In addition to comparisons between the two groups, correlation analysis was performed between ferritin–cardiac T2* MRI results and echocardiographic parameters and age in TM patients. Results: Our study showed growth retardation (low height standard deviation score (SDS), low weight SDS and low BMI SDS), dilatation of the left cavities (high left ventricular internal diameter end diastole (LVIDd)), increased left ventricular muscle mass (high left ventricular mass index (LVMI)), cardiac distinctive diastolic (restrictive pattern: left ventricular (LV) peak early diastolic flow (E)/peak late diastolic flow (A) and E/early diastolic myocardial peak flow (E') high), and subclinical systolic (LV peak systolic flow low and LV Tei index high) dysfunction. In addition, iron load (ferritin and cardiac T2* MRI) was correlated with LVMI, and cardiac diastolic and systolic function indicators. As age increased, ferritin value did not change, but cardiac T2* MRI value decreased and diastolic–systolic parameters worsened. Conclusion: Periodic cardiac T2* MRI and Doppler echocardiography examinations of patients with TM may detect subclinical myocardial dysfunction at an early stage, thus providing a window of opportunity for intervention.

Spectra of intracranial diseases in Chinese military pilots (cadets) unqualified for transfer to pilot modified high performance aircraft.

With very high mortality and disability rates, cerebrovascular diseases and intracranial tumors severely threaten the health and fighting strength of flying personnel, requiring great concern and intensive screening in clinic, early warning in an early and accurate manner and early intervention of diseases possibly resulting in inflight incapacitation are key emphases of aeromedical support in clinic. To probe into the spectra of intracranial diseases, flight factors and medical imaging characteristics of military pilots (cadets) in the physical examination for transfer to pilot modified high performance aircraft, thus rendering theoretical references for clinical aeromedical support of pilots. A total of 554 military pilots (cadets) undergoing physical examination for transfer to pilot modified high performance aircraft from December 2020 to April 2024 in a military medical center were enrolled in this study. Then, a retrospective study was carried out on intracranial disease spectra and head magnetic resonance imaging (MRI) data of 36 pilots (cadets) who were unqualified for transfer to pilot modified high performance aircraft. Besides, a descriptive statistical analysis was conducted on the clinical data, age, fighter type and head MRI data of such pilots (cadets). Abnormal head images were found in 36 out of 554 pilots (cadets) participating in the physical examination for transfer to pilot modified high performance aircraft, including arachnoid cyst in 17 (3.1%) military pilots (cadets), suspected very small aneurysm in 11 (2.0%), cavernous hemangioma in 4 (0.7%), vascular malformation in 2 (0.4%), and pituitary tumor in 3 (0.5%, one of which developed cavernous hemangioma simultaneously). Among the 17 pilots (cadets) with arachnoid cyst, 4 were identified as unqualified for transfer to pilot modified high performance aircraft because the marginal brain tissues were compressed by the cyst > 6 cm in length and diameter. The 11 pilots (cadets) with suspected very small aneurysms identified by 3.0T MRI consisted of 6 diagnosed with conus arteriosus by digital subtraction angiography and qualified for transfer to pilot modified high performance aircraft, and 5 identified as very small intracranial aneurysms with diameter < 3 mm and unqualified for transfer to pilot modified high performance aircraft. No symptoms and signs were observed in the 4 military pilots (cadets) with cavernous hemangioma, and the results of MRI revealed bleeding. The 1 of the 4 had the lesion located in pons and developed Rathke cyst in pituitary gland at the same time, and unqualified for transfer to pilot modified high performance aircraft. The 2 of the 4 were unqualified for flying, and 2 transferred to air combat service division. The 2 pilots (cadets) with vascular malformation were identified as unqualified for transfer to pilot modified high performance aircraft. Among the 3 pilots (cadets) with pituitary tumor, one pilot cadet was identified as unqualified for flying since the tumor compressed the optic chiasma, one had cavernous hemangioma in pons in the meantime and transferred to air combat service division, and one was diagnosed with nonfunctional microadenoma and qualified for transfer to pilot modified high performance aircraft. High-resolution head MRI examination is of great significance for screening and detecting cerebrovascular diseases and intracranial tumors in military flying personnel, and attention should be paid to its clinical application to physical examination for transfer to pilot modified high performance aircraft.

Single-Centre Analysis of Magnetic Resonance Imaging of Sacroiliac Joints in a Paediatric Population.

Background: Sacroiliitis in children is usually connected with one of the subtypes of juvenile idiopathic arthritis (JIA), such as enthesitis-related arthritis, psoriatic arthritis, or undifferentiated arthritis. The main diagnostic method is magnetic resonance imaging (MRI) of the sacroiliac joints, which can reveal bone marrow edema (BME) as a sign of an active inflammation process. This research aimed to retrospectively investigate the associations between the clinical presentation, laboratory test results, and MRI results of the sacroiliac joints of children. Methods: A total of 152 paediatric patients who underwent MRI of the sacroiliac joints were included in this single-centre study. The mean age of patients was 13.91 ± 2.97, while the female-to-male ratio was 1.36:1. JIA diagnosis was confirmed in 91 (59.87%) patients. Results: The main symptom reported by 128 (83.21%) patients was chronic pain, while in another 40 (31.25%) patients, it was chronic back pain. Patients with arthritis and BME in the sacroiliac joints were more likely to report chronic back pain, while patients with JIA but without BME in the sacroiliac joints were often positive for anti-nuclear antibodies (ANA). The widening of any joint contour was observed in 43 (28.29%) patients, and reduced joint mobility was observed in 61 (40.13%). Elevation of inflammatory blood parameters occurred in 31 (20.39%) patients, but this was not statistically related to BME presence in the sacroiliac joints. Radiological findings included BME (n = 36; 23.68% of examinations), joint space narrowing (n = 10; 27.78% of examinations), erosions (n = 7; 19.44% of examinations), and joint fluid (n = 7; 19.44% of examinations). There was a statistically significant relationship between the presence of BME in the sacroiliac joints and all of the above radiological findings. Conclusions: The radiological findings of MRI of the sacroiliac joints are significantly statistically related to chronic back pain in patients, while there is no relationship between any inflammatory blood parameter and the presence of BME.