Gd Enhancement Research Articles

TMIC-29. IMMUNE SPECIFIC IMAGING TECHNIQUES IN GLIOBLASTOMA: SELFI MRI IDENTIFIES AGGRESSIVE AND IMMUNOSUPPRESSIVE BIOLOGICAL FEATURES THAT CONTRIBUTE TO THERAPEUTIC RESISTANCE

Abstract Gadolinium (Gd) enhanced MRI is nonspecific for identifying aggressive glioblastoma biology. Glioblastoma-associated macrophages (GAMs) are pivotal in regrowth. Segregation and Extravascular Localization of Ferumoxytol Imaging (SELFI) is a quantitative immune specific MRI technique. SELFI+ values quantify M2 GAMs by phagocytized Ferumoxytol (Fe), while SELFI- values delineate intravascular Fe, cerebral blood volume. The relationship between SELFI and biology driving therapeutic resistance remains unknown. We aimed to determine if SELFI identified immunosuppressive GAMs and biology contributing to poor outcomes, a capability not yet achievable in clinical practice. This prospective study included four patients with glioblastoma. All underwent preoperative Gd and Fe (7 mg/kg up to 510 mg) enhanced MRI allowing for image guided biopsy based on Gd enhancement and FLAIR hyperintensity. RNA was analyzed on GeneChip Clariom Arrays. Intraoperative biopsy location was referenced to MRI for placement of volumes of interest (VOIs). VOIs quantified MRI phenotype and SELFI values. Gene Set Enrichment Analysis (GSEA) assessed differential expression between MRI features. T-test assessed differences in SELFI (p <0.05) and GSEA significance was assessed by normalized enrichment score (NES) and false discovery rate (FDR) q-value. Four patients provided 36 image guided tissue samples with sufficient quality to assess the causal relationships between MRI features and transcriptomics. Stratification by patient MGMT methylation status (N= 3 unmethylated) demonstrated Gd+ regions had significantly elevated SELFI+ values (Mean±SD, Gd+ = 0.24±0.17, Gd- = 0.08±0.09, P<0.01). GSEA demonstrated that tissues with elevated SELFI+ and lowered SELFI- values were comprised of significantly upregulated hypoxia and transforming growth factor-beta (TGFβ) signaling; among others (NES>1.5, FDR q-value<0.05). SELFI MRI uniquely quantifies glioblastoma by localizing sites of biological aggressiveness known to contribute to therapeutic resistance and disease recurrence. Patient enrollment continues to further define the causal relationships between SELFI, GAMs, and glioblastoma biology.

In situ optical feedback in brain tumor biopsy - a multipara-metric analysis

Abstract Introduction Brain tumor needle biopsy interventions are inflicted with non-diagnostic or biased sampling in up to 25% and hemorrhage, including asymptomatic cases, in up to 60%. To identify diagnostic tissue and sites with increased microcirculation, intraoperative optical techniques have been suggested. The aim of this study was to investigate the clinical implications of in situ optical guidance in frameless navigated tumor biopsies. Methods Real-time feedback on protoporphyrin IX (PpIX) fluorescence, microcirculation, and gray-whiteness was given before tissue sampling (272 positions) in 20 patients along 21 trajectories in total. The primary variables of investigation were fluorescence in relation to neuropathological findings and gadolinium (Gd) enhancement, increased cerebral microcirculation in relation to bleeding incidence, number of trajectories, and impact on operation time. Results PpIX fluorescence was detected in Glioblastoma IDH-wildtype CNS WHO grade 4 (n=12), Primary diffuse large B-cell lymphoma (n=3), astrocytoma IDH-mutated CNS WHO grade 4 (n=1) (Ki67 indices ≥15%). For two patients, no PpIX fluorescence or Gd was found, although samples contained tumorous tissue (Ki67 index 6%). Increased microcirculation was found along nine trajectories (34 sites), located in cortical, tumorous, or tentorium regions. Postoperative bleedings (n=10, nine asymptomatic) were related to skull opening or tissue sampling. The present study strengthens the proposed independence from intraoperative neuropathology as PpIX fluorescence is detected. Objective real-time feedback resulted in fewer trajectories compared to previous studies indicating reduced operation time. Conclusions The integrated optical guidance system provides real-time feedback in situ, increasing certainty and precision of diagnostic tissue before sampling during frameless brain tumor biopsies.

Multi-echo three-dimensional (3D) Dixon sequence combined with disodium gadolinium for risk stratification of advanced fibrosis in metabolic dysfunction-associated steatotic liver disease.

The hepatic steatosis and fibrosis related to metabolic dysfunction-associated steatotic liver disease (MASLD) are important factors in the progression. The Multi echo three-dimensional (3D) Dixon sequence can obtain a single breath hold scan for a fat fraction map and an R2* map. The R2* value is usually used to evaluate iron deposition. Whether the change in R2* value is related to liver fibrosis after injection of gadolinium disulfide (Gd) should be noted. This study evaluates the value of enhanced magnetic relaxation time in the risk stratification of liver fibrosis by analyzing the changes in R2* before and after Gd enhancement, and explores the potential application of Multi echo 3D Dixon sequence in one-stop evaluation of MASLD. This retrospective study included 138 MASLD patients who underwent Gadolinum ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI) examination in The First Affiliated Hospital of Chongqing Medical University from June 2020 to December 2021. Finally, 90 subjects were divided into moderate and high-risk fibrosis group and low-risk fibrosis group by two-step assessment of liver fibrosis. Multi-echo 3D chemical shift imaging sequence (Q-Dixon) sequences and gradient-echo T1WI (Vibe-Dixon) sequence were performed during the non-enhanced phase and hepatobiliary phase, respectively, and then the signal-intensity enhancement (SE) and magnetic relaxation-time enhancement (RE) values were calculated. The interobserver correlation coefficient was used to evaluate the consistency between observers. Univariate t-test was used to analyze the differences in RE and SE of liver fibrosis among different risk levels. Delong analysis was performed on receiver operating characteristic (ROC) curve to evaluate the difference in diagnostic efficacy between RE and SE in differentiating the risk level of liver fibrosis. Among the 90 patients, 55 (61.1%) belonged to the low-risk group and 35 (38.9%) belonged to the medium-to-high-risk group. The average RE and SE values were 1.23±0.15 and 1.57±0.23 in the low-risk group and 0.99±0.09 and 1.38±0.21 in both the medium-to-high-risk group (P<0.01). The ROC curve showed that the area under the curve (AUC) value of RE was 0.922, with a corresponding optimal threshold of 0.713, sensitivity of 0.852, and specificity of 0.861. The AUC value of SE was 0.724, with a corresponding optimal threshold of 0.352, sensitivity of 0.519, and specificity of 0.833. The AUC difference between RE and SE for the predictive value of different risk assessments was 0.198, and the 95% confidence interval of the difference was 0.084-0.312. The Delong test showed that the difference was significant (P<0.01). Magnetic RE had high effectiveness for distinguishing between liver-fibrosis risk levels. The combination of the Q-Dixon sequence and Gd-EOB-DTPA has the potential of one-stop evaluation of MASLD.

The feasibility of half-dose contrast-enhanced scanning of brain tumours at 5.0 T: a preliminary study

PurposeThis study investigated and compared the effects of Gd enhancement on brain tumours with a half-dose of contrast medium at 5.0 T and with a full dose at 3.0 T.MethodsTwelve subjects diagnosed with brain tumours were included in this study and underwent MRI after contrast agent injection at 3.0 T (full dose) or 5.0 T (half dose) with a 3D T1-weighted gradient echo sequence. The postcontrast images were compared by two independent neuroradiologists in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and subjective image quality score on a ten-point Likert scale. Quantitative indices and subjective quality ratings were compared with paired Student's t tests, and interreader agreement was assessed with the intraclass correlation coefficient (ICC).ResultsA total of 16 enhanced tumour lesions were detected. The SNR was significantly greater at 5.0 T than at 3.0 T in grey matter, white matter and enhanced lesions (p < 0.001). The CNR was also significantly greater at 5.0 T than at 3.0 T for grey matter/tumour lesions, white matter/tumour lesions, and grey matter/white matter (p < 0.001). Subjective evaluation revealed that the internal structure and outline of the tumour lesions were more clearly displayed with a half-dose at 5.0 T (Likert scale 8.1 ± 0.3 at 3.0 T, 8.9 ± 0.3 at 5.0 T, p < 0.001), and the effects of enhancement in the lesions were comparable to those with a full dose at 3.0 T (7.8 ± 0.3 at 3.0 T, 8.7 ± 0.4 at 5.0 T, p < 0.001). All subjective scores were good to excellent at both 5.0 T and 3.0 T.ConclusionBoth quantitative and subjective evaluation parameters suggested that half-dose enhanced scanning via 5.0 T MRI might be feasible for meeting clinical diagnostic requirements, as the image quality remains optimal. Enhanced scanning at 5.0 T with a half-dose of contrast agents might benefit patients with conditions that require less intravenous contrast agent, such as renal dysfunction.

Multiple dural arteriovenous fistulas showing isolated subcortical white matter T2 hyperintensity with gadolinium enhancement

We describe a 44-year-old man with a complaint of atonic seizures of the left upper limb, followed by generalized seizures. Brain MRI showed isolated juxtacortical white matter T2 hyperintensity with gadolinium (Gd) enhancement of the adjacent cortical gray matter and subcortical white matter in the right frontal convexity. Treatment with levetiracetam was effective for seizure suppression, and he had no other neurological abnormalities. Human leukocyte antigen typing revealed B54 and Cw1, which indicated the possibility of neuro-Sweet disease. However, a general examination, which included vital signs and eye and skin findings, was normal. A cerebrospinal fluid test showed a mild elevation in protein levels without pleocytosis and a normal range of interleukin-6. Electroencephalography showed intermittent slow waves without epileptic discharge in the bilateral temporal lobes. We detected subtle flow voids in the pia mater of the left frontal lobe, which suggested cerebrovascular disease, and specifically, the possibility of dural arteriovenous fistulas. Computed tomography angiography showed abnormally dilated perimedullary veins in the left frontal lobe. Cerebral angiography confirmed the existence of four dural arteriovenous fistulas, which included two retrograde leptomeningeal venous drainages in the right frontal cortical veins supplied by the anterior branch of the right middle meningeal artery. The other dural arteriovenous fistulas were retrograde leptomeningeal venous drainages in the left frontal cortical veins supplied by the anterior and posterior convexity branches of the left middle meningeal artery. The patient underwent successful endovascular embolization of all dural arteriovenous fistulas with Onyx injection. A follow-up MRI showed gradual improvement of the T2 hyperintensity and Gd enhancement. He remained seizure-free for 2 years following endovascular embolization.

A Case with Anti-ganglioside Antibodies Showing Multiple Cranial Nerve Palsies Detected on Gadolinium-enhanced Magnetic Resonance Imaging.

The anti-GQ1b IgG antibody is often accompanied by other anti-ganglioside antibodies, which induces various neurological symptoms. We herein report a patient with anti-ganglioside antibodies, including anti-GQ1b IgG and anti-GT1a IgG antibodies, showing bilateral ophthalmoplegia, facial nerve palsies, dysarthria, dysphagia, dysesthesia in both hands, and enhancement of the bilateral oculomotor, abducens, and facial nerves on gadolinium (Gd)-enhanced T1-weighted brain magnetic resonance imaging (MRI). He was first treated with intravenous immunoglobulin, which improved ophthalmoplegia, bulbar palsies, and dysesthesia of hands, but the facial nerve palsies worsened, and Gd enhancement of the brain nerves persisted. High-dose methylprednisolone therapy subsequently improved the facial nerve palsies and Gd enhancement of the cranial nerves. This is the first case with anti-ganglioside antibodies presenting with multiple cranial nerve palsies that was followed to track the changes in the Gd enhancement of cranial nerves on MRI.

New Enhancing MRI Lesions Associate with IL-17, Neutrophil Degranulation and Integrin Microparticles: Multi-Omics Combined with Frequent MRI in Multiple Sclerosis.

Blood-barrier (BBB) breakdown and active inflammation are hallmarks of relapsing multiple sclerosis (RMS), but the molecular events contributing to the development of new lesions are not well explored. Leaky endothelial junctions are associated with increased production of endothelial-derived extracellular microvesicles (EVs) and result in the entry of circulating immune cells into the brain. MRI with intravenous gadolinium (Gd) can visualize acute blood-barrier disruption as the initial event of the evolution of new lesions. Here, weekly MRI with Gd was combined with proteomics, multiplex immunoassay, and endothelial stress-optimized EV array to identify early markers related to BBB disruption. Five patients with RMS with no disease-modifying treatment were monitored weekly using high-resolution 3T MRI scanning with intravenous gadolinium (Gd) for 8 weeks. Patients were then divided into three groups (low, medium, or high MRI activity) defined by the number of new, total, and maximally enhancing Gd-enhancing lesions and the number of new FLAIR lesions. Plasma samples taken at each MRI were analyzed for protein biomarkers of inflammation by quantitative proteomics, and cytokines using multiplex immunoassays. EVs were characterized with an optimized endothelial stress EV array based on exosome surface protein markers for the detection of soluble secreted EVs. Proteomics analysis of plasma yielded quantitative information on 208 proteins at each patient time point (n = 40). We observed the highest number of unique dysregulated proteins (DEPs) and the highest functional enrichment in the low vs. high MRI activity comparison. Complement activation and complement/coagulation cascade were also strongly overrepresented in the low vs. high MRI activity comparison. Activation of the alternative complement pathway, pathways of blood coagulation, extracellular matrix organization, and the regulation of TLR and IGF transport were unique for the low vs. high MRI activity comparison as well, with these pathways being overrepresented in the patient with high MRI activity. Principal component analysis indicated the individuality of plasma profiles in patients. IL-17 was upregulated at all time points during 8 weeks in patients with high vs. low MRI activity. Hierarchical clustering of soluble markers in the plasma indicated that all four MRI outcomes clustered together with IL-17, IL-12p70, and IL-1β. MRI outcomes also showed clustering with EV markers CD62E/P, MIC A/B, ICAM-1, and CD42A. The combined cluster of these cytokines, EV markers, and MRI outcomes clustered also with IL-12p40 and IL-7. All four MRI outcomes correlated positively with levels of IL-17 (p < 0.001, respectively), and EV-ICAM-1 (p < 0.0003, respectively). IL-1β levels positively correlated with the number of new Gd-enhancing lesions (p < 0.01), new FLAIR lesions (p < 0.001), and total number of Gd-enhancing lesions (p < 0.05). IL-6 levels positively correlated with the number of new FLAIR lesions (p < 0.05). Random Forests and linear mixed models identified IL-17, CCL17/TARC, CCL3/MIP-1α, and TNF-α as composite biomarkers predicting new lesion evolution. Combination of serial frequent MRI with proteome, neuroinflammation markers, and protein array data of EVs enabled assessment of temporal changes in inflammation and endothelial dysfunction in RMS related to the evolution of new and enhancing lesions. Particularly, the Th17 pathway and IL-1β clustered and correlated with new lesions and Gd enhancement, indicating their importance in BBB disruption and initiating acute brain inflammation in MS. In addition to the Th17 pathway, abundant protein changes between MRI activity groups suggested the role of EVs and the coagulation system along with innate immune responses including acute phase proteins, complement components, and neutrophil degranulation.

Attenuation of gadolinium enhancement in pituitary gland on magnetic resonance imaging of patients with pediatric growth hormone deficiency

BackgroundAlthough it is generally thought that disturbance of perfusion in the anterior lobe of the pituitary gland leads to complete or partial hypopituitarism, the gadolinium (Gd) enhancement findings on Magnetic Resonance Imaging (MRI) of patients with growth hormone deficiency (GHD) remain unknown. The purpose of this study was to compare Gd enhancement of the pituitary gland on MRI of patients with GHD to that of healthy subjects.MethodsIn this retrospective study, we analyzed the data of 10 patients with clinically diagnosed GHD who underwent Gd-enhanced MRI of their pituitaries (age 8.3pm3.5 year, female 1, males 9), together with data of 5 patients with clinically normal growth hormone (GH) dynamics who also underwent Gd-enhanced pituitary MRI (age 6.2pm3.4 year, female 4, males 1). In each subject, a maximum-diameter region of interest (ROI) was drawn on the anterior pituitary gland of post Gd-enhanced coronal T1-weighted images, and the signal intensity ratio of the anterior pituitary gland to the white matter on the right temporal lobe of the same cross section was assessed.ResultsThe mean area of the ROI in the anterior pituitary gland and white matter of temporal lobe on the same cross section showed no significant differences between patients with GHD and those with normal GH (pituitary, 17.43 mm2pm8.24 vs. 21.08 mm2pm10.40, p = 1.00; white matter, 74.47mm2pm24.19 and 62.50 mm2pm17.90, p = 0.37), suggesting that the sizes of the pituitary glands were comparable. The ratios of Gd enhancement in the anterior pituitary gland showed significant differences between GHD and normal-GH subjects (pm0.716pm0.68pm0.26 vs.0.72pm0.16, p= 0.04).ConclusionsThese results suggested that the contrast effect on Gd-enhanced MRI is attenuated in the pituitary glands of patients with GHD compared to those with normal GH. These new clinical findings regarding Gd-enhanced MRI can assist the diagnosis of pediatric GHD.

Long-term effects of natalizumab on MRI activity and clinical outcomes in Japanese patients with relapsing-remitting multiple sclerosis

BackgroundRelapsing-remitting multiple sclerosis (RRMS) is the most common phenotype of multiple sclerosis (MS), and its active stage is characterized by active T2 lesions with or without gadolinium (Gd) enhancement on magnetic resonance imaging (MRI). Natalizumab is indicated as monotherapy in adults with active RRMS in Japan. The main objective of this study was to investigate the long-term effect of natalizumab on disease progression in Japanese patients with RRMS using MRI data.MethodsThis retrospective, chart review study was conducted at a single center in Japan. The main study outcome was the yearly proportion of patients with active T2-weighted image lesions detected with or without Gd enhancement on brain MRI (incidence rate) after treatment initiation for up to 5 years. Additional endpoints included annual relapse rate (ARR) and expanded disability status scale (EDSS) score.ResultsThis study included data from 85 patients with RRMS who had received natalizumab for ≥ 1 year; of these, 65 (76.5%) were female and the mean ± standard deviation (SD) age at baseline was 37.5 ± 10.0 years. The incidence rate of active T2 lesions was 52.9% (45/85) in the year prior to natalizumab treatment (Year − 1), which decreased to 2.4% and 1.6% in Year 0.5–1.5 and Year 1.5–2.5, respectively. No active T2 lesions were detected in Year 2.5–5.5 in patients who continued natalizumab treatment. EDSS score was stable, improved, and worsened in 61.8%, 26.3%, and 11.8% of patients, respectively. The median (range) EDSS score was 2.0 (0.0–7.0) at baseline (n = 85) and remained within a similar range (median score between 1.0 and 2.25 during Years 1–5). ARR decreased from 1.12 relapses per year at baseline to 0.12 relapses per year during Year 1 and remained below 0.15 relapses per year up to Year 5.ConclusionThe results of this first long-term study evaluating the effect of natalizumab on MRI activity and clinical outcomes in Japanese patients with RRMS suggest that natalizumab markedly reduced disease activity and maintained effectiveness over several years.

Menière's Syndrome Associated With Fibrous Dysplasia of the Temporal Bone.

Menière's Syndrome Associated With Fibrous Dysplasia of the Temporal Bone.

The Use of Disease-Modifying Therapy (DMT) to Prevent Disability Progression in Patients with Multiple Sclerosis (MS) in Thailand

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that leads to significant disability and economic burden for patients, families, the health system, and society. Objective: To describe the demographics, natural history, and effectiveness of disease-modifying therapies (DMTs) in MS patients. Materials and Methods: The present study was a retrospective cohort study of patients diagnosed with MS at the Prasat Neurological Institute, a tertiary referral neurological center in Bangkok, Thailand, between June 1, 2010 and June 30, 2020. Demographic data, clinical characteristics, and disease course of MS patients were explored. The primary outcome of the present study was a comparison of time to events of clinical relapse, new magnetic resonance image (MRI) T2W activity, new MRI T1W with gadolinium (Gd) enhancement, and time to disability progression between patients who received DMT and patients without DMT. Results: There were 102 patients diagnosed with MS. The female-to-male ratio was 2.4-to-1. The mean age at onset was 29.61±11.62 years. The phenotypic features of these patients were classified as RRMS 80.4%, SPMS 8.8%, PPMS 3.9%, and tumefactive demyelination 6.9%. Forty-eight patients (47.1%) received DMT, 28 (58.3%) received IFN-beta, 11 (22.9%) received fingolimod, seven (14.6%) received teriflunomide, and two (4.2%) received rituximab. Results demonstrated that patients who did not received DMT had significantly more clinical disability compared to patients who received DMT (HR 2.97; 95% CI 1.01 to 8.73; p=0.048). However, the times to clinical relapse and MRI activity, including new T2W and new T1W Gd enhancing lesion, were not significantly different between the two groups. Conclusion: Patients with a relapsing-remitting phenotype tended to progress to severe disability within ten years. Treatment with DMT may delay disability progression in patients with MS. Keywords: Multiple sclerosis (MS); Disease-modifying therapy (DMT)

Deciphering spatially distinct immune microenvironments in glioblastoma using ferumoxytol and gadolinium-enhanced and FLAIR hyperintense MRI phenotypes

Abstract Background MRI with gadolinium (Gd)-contrast agents is used to assess glioblastoma treatment response but does not specifically reveal heterogeneous biology or immune microenvironmental composition. Ferumoxytol (Fe) contrast is an iron nanoparticle that localizes glioblastoma macrophages and microglia. Therefore, we hypothesized that the use of Fe contrast improves upon standard Gd-based T1-weighted and T2/FLAIR analysis by specifically delineating immune processes. Methods In this, HIPAA-compliant institutional review board-approved prospective study, stereotactic biopsy samples were acquired from patients with treatment-naïve and recurrent glioblastoma based on MR imaging phenotypes; Gd and Fe T1 enhancement (Gd+, Fe+) or not (Gd–, Fe–), as well as T2-Flair hyperintensity (FLAIR+, FLAIR–). Analysis of genetic expression was performed with RNA microarrays. Imaging and genomic expression patterns were compared using false discovery rate statistics. Results MR imaging phenotypes defined a variety of immune pathways and Hallmark gene sets. Gene set enrichment analysis demonstrated that Gd+, Fe+, and FLAIR+ features were individually correlated with the same 7 immune process gene sets. Fe+ tissue showed the greatest degree of immune Hallmark gene sets compared to Gd+ or Flair+ tissues and had statistically elevated M2 polarized macrophages, among others. Importantly, the FLAIR+ Gd+ and Fe– imaging phenotypes did not demonstrate expression of immune Hallmark gene sets. Conclusions Our study demonstrates the potential of Fe and Gd-enhanced MRI phenotypes to reveal spatially distinct immune processes within glioblastoma. Fe improves upon the standard of care Gd enhancement by specifically localizing glioblastoma-associated inflammatory processes, providing valuable insights into tumor biology.

PATH-23. HIGHLY INFILTRATING OLIGODENDROGLIOMAS SHOW DIFFERENT MORPHOLOGY FROM TYPICAL OLIGODENDROGLIOMAS WHILE MAINTAINING GOOD RESPONSE TO CHEMO-RADIATION THERAPY

Abstract Oligodendrogliomas are diffuse gliomas located in the cerebral hemisphere, and the MRI typically show swollen cortex and subcortical white matter by the tumor cells. IDH mutation and 1p/19q co-deletion define oligodendrogliomas in WHO classification, and these genetic alterations are associated with good response to chemo-radiation therapy and better prognosis compared to the IDH-mutant astrocytomas. We reviewed MRI findings of 60 oligodendrogliomas with 1p/19q co-deleted tumors which were diagnosed at Dokkyo Medical University since 1999. Of those, 3 cases showed highly infiltrating pattern in which tumors were more predominant in the white matter than the cortex and the infiltration involved multiple lobes. We retrospectively investigated those 3 cases for histological features, treatment, and clinical outcome. There were 2 males and 1 female. MRI showed faint-brushed Gd enhancement around the center of the tumor-infiltrated area in 1 case, while there was no enhancing lesion in other 2 cases. All three underwent stereotactic biopsy. Histologically, all 3 cases lacked typical oligodendroglioma morphology: the tumor cells have irregular round, oval to elongated nuclei without perinuclear halo and had dense, closed chromatin similar to astrocytoma. Two cases underwent chemotherapy (TMZ and PAV accordingly), without radiation and 1 case underwent chemotherapy with radiation as the primary treatment. Interestingly, all three tumors responded well not only to the primary treatments but also to the radiation therapy administered after recurrence, although all eventually succumbed to the tumor. PFS were 16, 37, 67 months and OS were 104, 70, 115 months for each, which were at the worse end as oligodendrogliomas but are apparently better than astrocytomas. Highly infiltrating oligodendrogliomas appeared to show significantly different MRI and histological features from typical oligodendrogliomas that primarily involve cerebral cortex. The underlying mechanism of such differences might involve specific genetic alterations and/or gene expression alterations that may not affect treatment response.

Typical and atypical phenotype and neuroimaging of X-linked adrenoleukodystrophy in a Chinese cohort.

The objective of this study is to describe the typical and atypical clinical and neuroimaging features of ALD in Chinese patients, which will help early diagnosis and intervention to improve prognosis of ALD. Forty-one patients in the Leukoencephalopathy Clinic of Neurology Department, Peking Union Medical College Hospital were enrolled. Detailed clinical manifestations and MRI features were analyzed. The relationship between phenotype and genotype as well as biochemical analysis was observed. The patients were classified according to phenotype and onset age, including 14 childhood cerebral ALD (CCALD), 8 adolescent cerebral ALD (adoCALD), 3 adult cerebral ALD (ACALD), 14 adrenomyeloneuropathy (AMN), and 2 ALD in women. AMN was the main presentation in adults. Visual impairment was usual onset symptom in CCALD and cognitive decline and psychiatric symptoms were found in adoCALD and ACALD. Typical MRI feature of CALD was symmetrical peri-ventricular "butterfly wings" like lesions in frontal and/or occipital lobe with peripheral DWI hyperintensities and Gd enhancement. Corpus callosum and internal capsule were always involved. Unilateral lesions were also possible. Cerebral AMN presented with centrum semiovale diffuse involvement. Spinocerebellar variant was a special subtype of AMN with obvious cerebellar and brainstem lesions. No relationships between phenotype and genotype as well as biochemical VLCFAs analysis were found. We emphasize that corpus callosum and internal capsule are always involved in ALD. A unilateral lesion is also possible. Neuroimaging of cerebral AMN is different from typical CALD with more centrum semiovale involvement. We support spinocerebellar variant was a rare subtype of AMN.

GLINT: GlucoCEST in neoplastic tumors at 3\xa0T\u2014clinical results of GlucoCEST in gliomas

ObjectiveClinical relevance of dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) imaging has mostly been demonstrated at ultra-high field (UHF) due to low effect size. Results of a cohort study at clinical field strength are shown herein.Materials and methodsMotion and field inhomogeneity corrected T1ρ‐based DGE (DGE⍴) images were acquired before, during and after a d-glucose injection with 6.3 s temporal resolution to detect accumulation in the brain. Six glioma patients with clear blood–brain barrier (BBB) leakage, two glioma patients with suspected BBB leakage, and three glioma patients without BBB leakage were scanned at 3 T.ResultsIn high-grade gliomas with BBB leakage, d-glucose uptake could be detected in the gadolinium (Gd) enhancing region as well as in the tumor necrosis with a maximum increase of ∆DGE⍴ around 0.25%, whereas unaffected white matter did not show any significant DGE⍴ increase. Glioma patients without Gd enhancement showed no detectable DGE⍴ effect within the tumor.ConclusionFirst application of DGE⍴ in a patient cohort shows an association between BBB leakage and DGE signal irrespective of the tumor grade. This indicates that glucoCEST corresponds more to the disruptions of BBB with Gd uptake than to the molecular tumor profile or tumor grading.

Factors Influencing the Degree of Disability in Patients With Multiple Sclerosis.

Objective: To explore the factors influencing the degree of disability in patients with multiple sclerosis (MS), and to provide evidence for its early diagnosis, prognostic evaluation and clinical intervention.Methods: This retrospective observational study included 72 patients with relapsing-remitting multiple sclerosis (RRMS) at the First Hospital of Shanxi Medical University. All patients completed craniocerebral and spinal cord MRI (with or without Gd enhancement) and were evaluated for Expanded Disability Status Score (EDSS) scores before receiving treatment.Results: Among 72 patients with RRMS, 45 (62.5%) had an EDSS score ≤3; A total of 27 patients (37.5%) had an EDSS score >3 points. Univariate analysis showed that age, annual recurrence rate (ARR), drug use, albumin (ALB), triglycerides (TG), and total number of lesions in groups with EDSS score ≤3 were significantly different from those with an EDSS score > 3 points (P < 0.05). Multivariate logistic regression analysis showed that ALB, total number of lesions, and drug use were independent influencing factors of the degree of disability in patients with MS, and the difference was statistically significant (P < 0.05). An ROC curve was constructed using ALB and the total number of lesions. The AUC of ALB was 0.681, P < 0.05, and the best cut-off value was 44.2 g/L. Its sensitivity to predict the degree of disability in patients with multiple sclerosis was 85.2%, while its specificity was 51.1%. The AUC of the total number of lesions was 0.665 (P < 0.05) and the best cut-off value was 5.5. Its sensitivity to predict the degree of disability in patients with multiple sclerosis was 70.4%, while its specificity was 64.4%. The AUC of the combined ALB, total number of lesions, and drug use was 0.795 (P < 0.05), sensitivity was 77.8, and specificity was 73.3%. The optimal diagnostic cut-off value of the regression equation for the EDSS score of patients with multiple sclerosis was 0.420.Conclusion: Serum ALB, total number of lesions, and drug use in patients with multiple sclerosis were independent factors influencing the degree of disability. These findings provide clinical evidence for the prognostic evaluation and early intervention of patients with multiple sclerosis.

High-Molecular-Weight Hyaluronic Acid Vehicle Can Deliver Gadolinium Into the Cochlea at a Higher Concentration for a Longer Duration: A 9.4-T Magnetic Resonance Imaging Study.

Intratympanic (IT) gadolinium (Gd) injection is one method of delivering Gd into the inner ear to evaluate the amount of endolymphatic hydrops (EH) using magnetic resonance imaging (MRI). As Gd is usually prepared in a fluid form mixed with saline, Gd injected into the middle ear drains easily through the Eustachian tube within several hours. High-molecular-weight (hMW) hyaluronic acid (HA) is an ideal vehicle for IT Gd due to its viscous and adhesive properties. The present study was performed to elucidate whether novel hMW HA is superior to conventional HA in delivering Gd into the inner ear in the short term. The second aim was to verify the long-term Gd delivery efficiency of hMW HA compared to the standard-of-care vehicle (saline). IT Gd injection and 3D T1-weighted MRI were performed in 13 rats. For the short-term study (imaging after 1, 2, and 3 h), the left ear was treated with hMW HA+Gd and the right ear with conventional HA+Gd. For the long-term study (imaging after 1, 2, 3, and 4 h, 1 – 3 days, and 7 – 10 days), the left ear was treated with hMW HA+Gd and the right ear with saline+Gd. Signal intensities (SIs) in the scala tympani (ST) and scala vestibuli (SV) were quantified. Compared to conventional HA, signal enhancement was 2.3 – 2.4 times greater in the apical and middle turns after hMW HA+Gd injection (SV at 1 h). In comparison to the standard-of-care procedure, the SI was not only greater in the short term but the higher SI also lasted for a longer duration. On days 7 – 10 after IT Gd delivery, the SI in the basal turn was 1.9 – 2.1 times greater in hMW HA+Gd-treated ears than in saline IT Gd-treated ears. Overall, hMW HA may be a useful vehicle for more efficient IT Gd delivery. Gd enhancement in the cochlea improved approximately two-fold when hMW HA was used. In addition, this greater enhancement lasted for up to 7 – 10 days. Repeated MRI of EH may be possible for several days with a single IT hMW HA+Gd delivery.

A phase I/IIa study to evaluate the safety and efficacy of blood-brain barrier (BBB) opening with the SonoCloud-9 implantable ultrasound device in recurrent glioblastoma patients receiving IV carboplatin.

2049 Background: Low intensity pulsed ultrasound (LIPU) in conjunction with intravenous microbubbles can transiently and reversibly disrupt the blood-brain barrier (BBB), allowing for an increase in the tissue concentration of chemotherapy agents in the brain. Mass spectrometry data from preclinical models (mouse, swine) showed a &gt; 5x enhancement in carboplatin brain concentrations, which correlated well with the spatial distribution of a Gadolinium (Gd) contrast agent used for magnetic resonance imaging (MRI). Methods: The primary objective of this phase I/IIa study (NCT03744026) was to demonstrate the safety of BBB disruption using LIPU in patients with recurrent glioblastoma. This study was a 3+3 design using escalating numbers (3, 6, 9) of activated 1 MHz ultrasound emitters. Nine patients were treated in the escalation phase and another 12 patients were treated with 9 emitters in the expansion phase. Eligibility included recurrent GBM (any recurrence) with a maximum tumor size of &lt; 70 mm. The SonoCloud-9 device (CarThera, Paris, France) was implanted during tumor debulking/resection surgery and replaced the bone flap, with the device targeting the tumor and surrounding peritumoral brain. The device was activated every four weeks for a duration of 270 seconds, concomitantly with IV DEFINITY microbubbles (10 ml/kg), to disrupt the BBB prior to administration of carboplatin (AUC 4-6). MRI was performed to verify safety and evaluate efficacy of BBB disruption with Gd enhancement. Results: No DLTs were observed. The overall tolerance of the SonoCloud-9 implant was good, with two transient, manageable grade 3 wound infections and one grade 1 acquired meningocele event considered as probably related to the overall procedure. The most frequent neurologic adverse events were grade 1 blurred vision (5%) and dizziness (5%). Conclusions: Significant Gd enhancement was observed after more than 90% of sonication sessions, suggesting effective BBB disruption and carboplatin enhancement. Clinical trial information: NCT03744026.

Correlation of 4\u2032-[methyl-11C]-thiothymidine PET with Gd-enhanced and FLAIR MRI in patients with newly diagnosed glioma

PurposeTo elucidate the biological association between tumor proliferation, tumor infiltration and neovascularization, we analyzed the association between volumetric information of 4′-[methyl-11C]thiothymidine (4DST) positron emission tomography (PET) and fluid-attenuated inversion recovery (FLAIR) and T1-weighted gadopentetate dimeglumine (Gd)-enhanced magnetic resonance imaging (MRI), in patients with newly diagnosed glioma.MethodsA total of 23 patients with newly diagnosed glioma who underwent both 4DST PET/CT and Gd-enhanced MRI before therapy were available for a retrospective analysis of prospectively collected data. The maximum standardized uptake value (SUVmax) for tumor (T) and the mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Proliferative tumor volume (PTV) from 4DST PET and the volume of Gd enhancement (GdV) and hyperintense region on FLAIR (FLAIRV) from MRI were calculated.ResultsAll gliomas but 3 diffuse astrocytomas and one anaplastic astrocytoma had 4DST uptake and Gd enhancement on MRI. There was no significant difference between PTV and GdV although the exact edges of the tumor differed in each modality. The FLAIRV was significantly larger than PTV (P < 0.001). Significant correlations between PTV and GdV (ρ = 0.941, P < 0.001) and FLAIRV (ρ = 0.682, P < 0.001) were found.ConclusionThese preliminary results indicate that tumor proliferation assessed by 4DST PET is closely associated with tumor-induced neovascularization determined by Gd-enhanced MRI in patients with newly diagnosed glioma.

Brain Calcification

Brain calcification can be either physiological or pathological. Pathological calcification occurs due to a wide spectrum of causes, including congenital disorders, infections, endocrine/metabolic diseases, cerebrovascular diseases, and neoplasms. The patient's age, localization of the calcification, and association with other imaging findings are useful for the correct diagnosis. Dural arteriovenous fistulas with cortical venous reflux should be included in the differential diagnosis of subcortical calcification via CT. MRA should be conducted subsequently. We recently reported the clinical and imaging characteristics of calcified brain metastases in 20 patients. Hemorrhage, necrosis, or degeneration were detected within the lesions in six patients. Both T1WI and T2WI showed a hyperintense mass surrounded by a hypointense rim in one patient. Hemorrhagic brain metastases can mimic cerebral cavernous malformations. Cancer metastasis should be considered as a differential diagnosis when calcified or hemorrhagic masses are detected in middle-aged and elderly patients. We recommend conducting MRI with Gd enhancement.