Magnetization Transfer Ratio Research Articles

Comparing myelin-sensitive magnetic resonance imaging measures and resulting g-ratios in healthy and multiple sclerosis brains

The myelin concentration and the degree of myelination of nerve fibers can provide valuable information on the integrity of human brain tissue. Magnetic resonance imaging (MRI) of myelin-sensitive parameters can help to non-invasively evaluate demyelinating diseases such as multiple sclerosis (MS). Several different myelin-sensitive MRI methods have been proposed to determine measures of the degree of myelination, in particular the g-ratio. However, variability in underlying physical principles and different biological models influence measured myelin concentrations, and consequently g-ratio values. We therefore investigated similarities and differences between five different myelin-sensitive MRI measures and their effects on g-ratio mapping in the brains of both MS patients and healthy volunteers.We compared two different estimates of the myelin water fraction (MWF) as well as the inhomogeneous magnetization transfer ratio (ihMTR), magnetization transfer saturation (MTsat), and macromolecular tissue volume (MTV) in 13 patients with MS and 14 healthy controls. In combination with diffusion-weighted imaging, we derived g-ratio parameter maps for each of the five different myelin measures.The g-ratio values calculated from different myelin measures varied strongly, especially in MS lesions. While, compared to normal-appearing white matter, MTsat and one estimate of the MWF resulted in higher g-ratio values within lesions, ihMTR, MTV, and the second MWF estimate resulted in lower lesion g-ratio values.As myelin-sensitive measures provide rough estimates of myelin content rather than absolute myelin concentrations, resulting g-ratio values strongly depend on the utilized myelin measure and model used for g-ratio mapping. When comparing g-ratio values, it is, thus, important to utilize the same MRI methods and models or to consider methodological differences. Particular caution is necessary in pathological tissue such as MS lesions.

Amide proton transfer-weighted magnetic resonance imaging for the diagnosis of symptomatic chronic intracranial artery stenosis: a feasibility study.

Hemodynamic changes after intracranial artery stenosis (ICAS) or occlusion are important causes of metabolic alterations in tissue. This study aimed to explore the feasibility of using amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI) to diagnose patients with symptomatic chronic ICAS based on pH variations caused by metabolite damage. Sixty-seven patients with clinically confirmed unilateral anterior circulation ICAS (≥70% arterial narrowing) and 20 healthy volunteers were recruited for the study. Each patient underwent an MRI examination including a T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence, spin-echo echo-planar diffusion-weighted imaging (DWI), three-dimensional pseudo-continuous arterial spin labeling (pcASL), and an APTw sequence. Areas with abnormal perfusion and APTw effects were defined as perfusion/pH matched areas; areas with abnormal perfusion but normal APTw effects were defined as perfusion/pH unmatched areas; the contralateral mirror areas were defined as the normal areas. Regions of interest (ROIs) were selected within these three areas, and the corresponding apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and magnetization transfer ratio asymmetry (MTRasym) were measured. High intraclass correlation coefficient (ICC) values (0.78≤ ICCs ≤0.97; P<0.05) were observed between the two radiologists who independently performed the data analysis. Significant differences were found in CBF and MTRasym between the perfusion/pH matched, perfusion/pH unmatched, and normal areas [F(2,64)=288.5, 163.5; both P<0.05], but the ADC values were comparable between the three [F(2,64)=2.11; P>0.05]. Spearman correlation analysis revealed no significant correlation between changes in MTRasym and CBF (P>0.05). Finally, APTw showed a robust performance in diagnosing symptomatic chronic ICAS, with an area under the receiver operating characteristic curve (ROC) of 0.953 (sensitivity 97.01%; specificity 85.07%; cut-off value 1.005%). The present study has demonstrated that metabolic alterations are present in patients with symptomatic chronic ICAS. Our findings illustrate that APTw imaging could potentially serve as an effective method to provide a robust clinical diagnosis for patients with symptomatic chronic ICAS.

Clinical and Research MRI Techniques for Assessing Spinal Cord Integrity in Degenerative Cervical Myelopathy-A Scoping Review.

Background: Degenerative cervical myelopathy (DCM) manifests as the primary cause of spinal cord dysfunction and is non-traumatic, chronic and progressive in nature. Decompressive surgery is typically utilised to halt further disability and neurological dysfunction. The limitations of current diagnostic options surrounding assessment and prognostic potential render DCM still largely a clinical diagnosis. Aims: To outline the limitations of current diagnostic techniques, present evidence behind novel quantitative MRI (qMRI) techniques for assessing spinal cord integrity in DCM and suggest future directions. Method: Articles published up to November 2021 were retrieved from Medline, EMBASE and EBM using key search terms: spinal cord, spine, neck, MRI, magnetic resonance imaging, qMRI, T1, T2, T2*, R2*, DTI, diffusion tensor imaging, MT, magnetisation transfer, SWI, susceptibility weighted imaging, BOLD, blood oxygen level dependent, fMRI, functional magnetic resonance imaging, functional MRI, MRS, magnetic resonance spectroscopy. Results: A total of 2057 articles were retrieved with 68 articles included for analysis. The search yielded 2 articles on Quantitative T1 mapping which suggested higher T1 values in spinal cord of moderate-severe DCM; 43 articles on DTI which indicated a strong correlation of fractional anisotropy and modified Japanese Orthopaedic Association scores; 15 articles on fMRI (BOLD) which demonstrated positive correlation of functional connectivity and volume of activation of various connections in the brain with post-surgical recovery; 6 articles on MRS which suggested that Choline/N-acetylaspartate (Cho/NAA) ratio presents the best correlation with DCM severity; and 4 articles on MT which revealed a preliminary negative correlation of magnetisation transfer ratio with DCM severity. Notably, most studies were of low sample size with short timeframes within 6 months. Conclusions: Further longitudinal studies with higher sample sizes and longer time horizons are necessary to determine the full prognostic capacity of qMRI in DCM.

Reassembled saturation transfer (REST) MR images at 2 B1 values for in vivo exchange-dependent imaging of amide and nuclear Overhauser enhancement.

Design an efficient CEST scheme for exchange-dependent images with high contrast-to-noise ratio. Reassembled saturation transfer (REST) signals were defined as r.Z=r.Zref - r.ZCEST and the reassembled exchange-dependen magnetization transfer ratio r.MTRRex =r.1/Zref - r.1/ZCEST , utilizing the averages over loosely sampled reference frequency offsets as Zref and over densely sampled target offsets as ZCEST . Using r.MTRRex measured under 2 B1,sat values, exchange rate could be estimated. The REST approach was optimized and assessed quantitatively by simulations for various exchange rates, pool concentration, and water T1 . In vivo evaluation was performed on ischemic rat brains at 7Tesla and human brains at 3Tesla, in comparison with conventional asymmetrical analysis, Lorentzian difference (LD), an MTRRex_ LD. For a broad choice of ranges and numbers, Δr.Z and r.MTRRex exhibited comparable quantification features with conventional LD and MTRRex _LD, respectively, when B1,sat ≤ 1μT. The subtraction of 2 REST values under distinct B1,sat values showed linear relationships with exchange rate and obtained immunity to field inhomogeneity and variation in MT and water T1 . For both rat and human studies, REST images exhibited similar contrast distribution to MTRRex _LD, with superiority in contrast-to-noise ratio and acquisition efficiency. Compared with MTRRex _LD, 2-B1,sat subtraction REST images displayed better resistance to B1 inhomogeneity, with more specific enhanced regions. They also showed higher signals for amide than for nuclear Overhauser enhancement effect in human brain, presumably reflecting the higher increment from faster-exchanging species as B1,sat increased. Featuring high contrast-to-noise ratio efficiency, REST could be a practical exchange-dependent approach readily applicable to either retrospective Z-spectra analysis or perspective 6-offset acquisition.

Chemical Exchange Saturation Transfer MRI for Differentiating Radiation Necrosis From Tumor Progression in Brain Metastasis-Application in a Clinical Setting.

High radiation doses of stereotactic radiosurgery (SRS) for brain metastases (BM) can increase the likelihood of radiation necrosis (RN). Advanced MRI sequences can improve the differentiation between RN and tumor progression (TP). To use saturation transfer MRI methods including chemical exchange saturation transfer (CEST) and magnetization transfer (MT) to distinguish RN from TP. Prospective cohort study. Seventy patients (median age 60; 73% females) with BM (75 lesions) post-SRS. 3-T, CEST imaging using low/high-power (saturation B1 =0.52 and 2.0 μT), quantitative MT imaging using B1 =1.5, 3.0, and 5.0 μT, WAter Saturation Shift Referencing (WASSR), WAter Shift And B1 (WASABI), T1 , and T2 mapping. All used gradient echoes except T2 mapping (gradient and spin echo). Voxel-wise metrics included: magnetization transfer ratio (MTR); apparent exchange-dependent relaxation (AREX); MTR asymmetry; normalized MT exchange rate and pool size product; direct water saturation peak width; and the observed T1 and T2 . Regions of interests (ROIs) were manually contoured on the post-Gd T1 w. The mean (of median ROI values) was compared between groups. Clinical outcomes were determined by clinical and radiologic follow-up or histopathology. t-Test, univariable and multivariable logistic regression, receiver operating characteristic, and area under the curve (AUC) with sensitivity/specificity values with the optimal cut point using the Youden index, Akaike information criterion (AIC), Cohen's d. P < 0.05 with Bonferroni correction was considered significant. Seven metrics showed significant differences between RN and TP. The high-power MTR showed the highest AUC of 0.88, followed by low-power MTR (AUC=0.87). The combination of low-power CEST scans improved the separation compared to individual parameters (with an AIC of 70.3 for low-power MTR/AREX). Cohen's d effect size showed that the MTR provided the largest effect sizes among all metrics. Significant differences between RN and TP were observed based on saturation transfer MRI. 3 Technical Efficacy: Stage 2.

Relationship between cerebrospinal fluid biomarkers of inflammation and tissue damage in primary progressive multiple sclerosis

Background and ObjectivesIt is unclear to what extent intrathecal inflammation contributes to the pathogenesis in primary progressive multiple sclerosis (PPMS). We conducted an exploratory study to investigate the degree of intrathecal inflammation and its association with biomarkers of disease activity and severity in patients with PPMS. MethodsWe included patients with PPMS who participated in a randomized controlled trial conducted at the Danish Multiple Sclerosis Center, patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls. We analyzed concentrations of a panel of cytokines in CSF using electrochemiluminescence assays. We then explored the relationship between cytokines found in increased CSF concentrations in patients with PPMS (compared with healthy controls) with CSF concentrations of neurofilament light chain (NFL) and myelin basic protein (MBP), IgG-index, and magnetic resonance imaging (MRI) metrics (volume, magnetization transfer ratio and diffusion tensor imaging) from lesions, normal-appearing white matter, and cortical grey matter. ResultsWe included 59 patients with PPMS, 40 patients with RRMS, and 21 healthy controls. In patients with PPMS, CSF concentrations of CC chemokine ligand 3 (CCL-3), CXC chemokine ligand 8 (CXCL-8), CXCL-10, interleukin (IL)-10, IL-15, and vascular endothelial growth factor (VEGF)-A were increased compared with healthy controls and comparable with CSF concentrations in patients with RRMS. In addition, patients with PPMS had increased CSF concentrations of IL-12p40, IL-17A, tumor necrosis factor (TNF)-α, and lymphotoxin (LT)-α compared with healthy controls, but concentrations of these cytokines were even higher in patients with RRMS. For the remaining seven cytokines (CCL22, interferon-γ, IL-5, IL-7, IL-16, IL-22, IL-27), we found no difference between patients with PPMS and healthy controls. CSF concentrations of NFL and MBP correlated weakly with concentrations of IL-15, while the remaining proinflammatory cytokines were not associated with CSF concentrations of NFL or MBP. The IgG-index correlated with four cytokines (IL-10, IL-12p40, TNF-α, and LT-α). We did not observe any significant associations between MRI metrics and CSF biomarkers of inflammation. DiscussionIn this exploratory study, we found few and weak associations between intrathecal inflammation and the extent of neuroaxonal damage and demyelination, and no associations between intrathecal inflammation and MRI metrics, in patients with PPMS. Our findings suggest that, for patients with PPMS, these measures of intrathecal inflammation are not associated with the extent of neuroaxonal injury, demyelination, and disease severity, and these processes may therefore have less relevance in PPMS than in relapsing forms of MS.

Differentiating Multiple Sclerosis From AQP4-Neuromyelitis Optica Spectrum Disorder and MOG-Antibody Disease With Imaging.

Relapsing-remitting multiple sclerosis (RRMS), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may have overlapping clinical features. There is an unmet need for imaging markers that differentiate between them when serologic testing is unavailable or ambiguous. We assessed whether imaging characteristics typical of MS discriminate RRMS from AQP4-NMOSD and MOGAD, alone and in combination. Adult, nonacute patients with RRMS, APQ4-NMOSD, and MOGAD and healthy controls were prospectively recruited at the National Hospital for Neurology and Neurosurgery (London, United Kingdom) and the Walton Centre (Liverpool, United Kingdom) between 2014 and 2019. They underwent conventional and advanced brain, cord, and optic nerve MRI and optical coherence tomography (OCT). A total of 91 consecutive patients (31 RRMS, 30 APQ4-NMOSD, and 30 MOGAD) and 34 healthy controls were recruited. The most accurate measures differentiating RRMS from AQP4-NMOSD were the proportion of lesions with the central vein sign (CVS) (84% vs 33%, accuracy/specificity/sensitivity: 91/88/93%, p < 0.001), followed by cortical lesions (median: 2 [range: 1-14] vs 1 [0-1], accuracy/specificity/sensitivity: 84/90/77%, p = 0.002) and white matter lesions (mean: 39.07 [±25.8] vs 9.5 [±14], accuracy/specificity/sensitivity: 78/84/73%, p = 0.001). The combination of higher proportion of CVS, cortical lesions, and optic nerve magnetization transfer ratio reached the highest accuracy in distinguishing RRMS from AQP4-NMOSD (accuracy/specificity/sensitivity: 95/92/97%, p < 0.001). The most accurate measures favoring RRMS over MOGAD were white matter lesions (39.07 [±25.8] vs 1 [±2.3], accuracy/specificity/sensitivity: 94/94/93%, p = 0.006), followed by cortical lesions (2 [1-14] vs 1 [0-1], accuracy/specificity/sensitivity: 84/97/71%, p = 0.004), and retinal nerve fiber layer thickness (RNFL) (mean: 87.54 [±13.83] vs 75.54 [±20.33], accuracy/specificity/sensitivity: 80/79/81%, p = 0.009). Higher cortical lesion number combined with higher RNFL thickness best differentiated RRMS from MOGAD (accuracy/specificity/sensitivity: 84/92/77%, p < 0.001). Cortical lesions, CVS, and optic nerve markers achieve a high accuracy in distinguishing RRMS from APQ4-NMOSD and MOGAD. This information may be useful in clinical practice, especially outside the acute phase and when serologic testing is ambiguous or not promptly available. This study provides Class II evidence that selected conventional and advanced brain, cord, and optic nerve MRI and OCT markers distinguish adult patients with RRMS from AQP4-NMOSD and MOGAD.

Quantitative spinal cord MRI and sexual dysfunction in multiple sclerosis.

BackgroundSexual dysfunction (SD) is frequently reported in multiple sclerosis (MS) and is likely related to MS-related damage to the spinal cord (SC).ObjectiveTo assess associations between SD and quantitative MRI measures in people with MS (pwMS).MethodsThis pilot study included 17 pwMS with SD who completed questionnaires assessing SD, mood, and fatigue. All participants underwent brain, cervical, and thoracic SC-MRI at 3T. Quantitative brain and SC-MRI measures, including brain/SC atrophy, SC lesion count, diffusion-tensor imaging (DTI) indices (fractional anisotropy [FA], mean, perpendicular, parallel diffusivity [MD, λ⊥, λ||]) and magnetization-transfer ratio (MTR) were obtained. Associations between quantitative MRI measures and SD were assessed while controlling for the extent of mood and fatigue symptomatology.ResultsSubjects were a mean age of 46.9 years and 29% female. All subjects had self-reported SD (MSISQ-19 = 40.7, SQoL: 55.9) and 65% had a concurrent psychiatric diagnosis. When correlations between SD severity were assessed with individual brain and SC-MRI measures while controlling for psychiatric symptomatology, no associations were found. The only variables showing independent associations with SD were anxiety (p = 0.03), depression (p = 0.05), and fatigue (p = 0.04).ConclusionWe found no correlations between quantitative MRI measures in the brain and SC and severity of SD in pwMS, but psychiatric symptomatology and fatigue severity demonstrated relationships with SD. The multifactorial nature of SD in pwMS mandates a multidisciplinary approach.

Remyelination varies between and within lesions in multiple sclerosis following bexarotene.

ObjectiveIn multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis. While the primary MRI outcome was negative, there was converging neurophysiological and MRI evidence of efficacy. Multiple factors influence lesion remyelination. In this study we undertook a systematic exploratory analysis to determine whether treatment response – measured by change in magnetisation transfer ratio – is influenced by location (tissue type and proximity to CSF) or the degree of abnormality (using baseline magnetisation transfer ratio and T1 values).MethodsWe examined treatment effects at the whole lesion level, the lesion component level (core, rim and perilesional tissues) and at the individual lesion voxel level.ResultsAt the whole lesion level, significant treatment effects were seen in GM but not WM lesions. Voxel‐level analyses detected significant treatment effects in WM lesion voxels with the lowest baseline MTR, and uncovered gradients of treatment effect in both WM and CGM lesional voxels, suggesting that treatment effects were lower near CSF spaces. Finally, larger treatment effects were seen in the outer and surrounding components of GM lesions compared to inner cores.InterpretationRemyelination varies markedly within and between lesions. The greater remyelinating effect in GM lesions is congruent with neuropathological observations. For future remyelination trials, whole GM lesion measures require less complex post‐processing compared to WM lesions (which require voxel level analyses) and markedly reduce sample sizes.

Early predictors of visual and axonal outcomes after acute optic neuritis.

BackgroundPredicting long-term visual outcomes and axonal loss following acute optic neuritis (ON) is critical for choosing treatment. Predictive models including all clinical and paraclinical measures of optic nerve dysfunction following ON are lacking.ObjectivesUsing a prospective study method, to identify 1 and 3 months predictors of 6 and 12 months visual outcome (low contrast letter acuity 2.5%) and axonal loss [retinal nerve fiber layer thickness and multifocal evoked potential (mfVEP) amplitude] following acute ON.MethodsIn total, 37 patients of acute ON onset were evaluated within 14 days using between-eye asymmetry of visual acuity, color vision (Ishihara plates), optical coherence tomography, mfVEP, and optic nerve magnetic resonance imaging [magnetic transfer ratio (MTR) and diffusion tensor imaging (DTI)].ResultsVisual outcome at 6 and 12 months was best predicted by Ishihara asymmetry at 1 and 3 months following ON onset. Axonal loss at 6 and 12 months was reliably predicted by Ishihara asymmetry at 1 month. Optic nerve MTR and DTI at 3 months post-acute ON could predict axonal loss at 6 and 12 months.ConclusionsSimple Ishihara asymmetry testing 1 month after acute ON onset can best predict visual outcome and axonal loss at 6 and 12 months in a clinical or research setting.

P15.12.A Amine CEST contrast in gliomas to measure metabolic treatment effect at 7T

Abstract Background Chemical exchange saturation transfer (CEST) is an imaging technique that generates contrast based on proton exchange between water and a solute pool of interest. CEST is sensitive to molecules containing amine groups such as glutamate and creatine. Since creatine is a crucial metabolite in cellular metabolism and deregulation in cellular bioenergetics is a hallmark of cancer, CEST could be relevant for glioma imaging, specifically when evaluating treatment response. No clear consensus has been established on its use, therefore we wanted to preliminarily investigate the presence of amine CEST contrast in the contrast enhanced (CE) and non-enhanced (NE) lesions of gliomas, and to assess whether treated tumors would display different CEST contrast compared to treatment naïve tumors. Material and Methods We prospectively scanned 12 glioma patients on a whole-body 7 Tesla Philips Achieva MRI scanner (7 treated glioblastomas; 4 treatment naïve glioblastomas; 1 treatment naïve low-grade astrocytoma). Treatment included surgical resection, chemotherapy and radiotherapy. All patients gave informed consent. CEST images were post-processed, including corrections for B0 and B1 inhomogeneities. The CEST Z-spectra and magnetization transfer ratio (MTR) asymmetry were calculated per voxel. To retrieve the CEST values within the tumor lesions and contralateral white matter for normalization, segmentations were manually delineated on the clinical T2-FLAIR or post contrast 3D-T1. Results Overall we observed a relative increase of amine CEST contrast in the CE (MTRasym: Mean (x̄)=1.32; Standard deviation (σ)= 0.28) compared to a relative decrease (MTRasym: x̄=1.20; σ= 0.35) in the NE lesion. When evaluating the results from the CE and NE lesions for treated and treatment naïve groups individually, we observed a slightly different trend. In the treatment group, the CE lesions showed a higher amine CEST contrast (MTRasym: x̄=1.38; σ= 0.30) than the NE (MTRasym: x̄ = 1.11; σ = 0.302). In contrast, in the treatment naïve group, the CE lesion showed a slightly lower CEST contrast (MTRasym: x̄ = 1.23; σ=0.21) than in the NE group (MTRasym: x̄ = 1.29; σ= 0.38). Conclusion Our results show different amine CEST contrast trends between treated and treatment naïve groups when comparing CE and NE lesions. This suggests that treatment may have an effect on tumor tissue bioenergetics affecting the concentration of creatine. Nevertheless, future work is necessary to verify our results in a larger group of patients.

Quantitative Chemical Exchange Saturation Transfer Imaging of Amide Proton Transfer Differentiates between Cerebellopontine Angle Schwannoma and Meningioma: Preliminary Results.

Vestibular schwannomas are the most common tumor at the common cerebellopontine angle, followed by meningiomas. Differentiation of these tumors is critical because of the different surgical approaches required for treatment. Recent studies have demonstrated the utility of amide proton transfer (APT)-chemical exchange saturation transfer (CEST) imaging in evaluating malignant brain tumors. However, APT imaging has not been applied in benign tumors. Here, we explored the potential of APT in differentiating between schwannomas and meningiomas at the cerebellopontine angle. We retrospectively evaluated nine patients with schwannoma and nine patients with meningioma who underwent APT-CEST MRI from November 2020 to April 2022 pre-operation. All 18 tumors were histologically diagnosed. There was a significant difference in magnetization transfer ratio asymmetry (MTRasym) values (0.033 ± 0.012 vs. 0.021 ± 0.004; p = 0.007) between the schwannoma and meningioma groups. Receiver operative curve analysis showed that MTRasym values clearly differentiated between the schwannoma and meningioma groups. At an MTRasym value threshold of 0.024, the diagnostic sensitivity, specificity, positive predictive value, and negative predictive values for MTRasym were 88.9%, 77.8%, 80.0%, and 87.5%, respectively. Our results demonstrated the ability of MTRasym values on APT-CEST imaging to discriminate patients with schwannomas from patients with meningiomas.

Sensitivity and specificity of amide proton transfer-weighted imaging for assessing programmed death-ligand 1 status in non-small cell lung cancer: a comparative study with intravoxel incoherent motion and 18F-FDG PET.

BackgroundNoninvasive assessment of programmed death-ligand 1 (PD-L1) expression status in non-small cell lung cancer (NSCLC) is necessary. This study arm to investigate the value of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET), diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and amide proton transfer-weighted imaging (APTWI) in the assessment of PD-L1 status in NSCLC.MethodsThis is a prospective diagnostic study. A total of 76 patients with NSCLC underwent chest 18F-FDG PET/magnetic resonance imaging (MRI). Parameters maximum standardized uptake value (SUVmax), quantitate the metabolic tumor volume (MTV), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f), and magnetization transfer ratio asymmetry at 3.5 ppm [MTRasym (3.5 ppm)] from 18F-FDG PET, DWI, IVIM, and APTWI, respectively, were compared. The optimal combination of parameters was investigated using logistic regression models and evaluated by area under the receiver operating characteristic (ROC) curve (AUC). The bootstrap with 1,000 samples was used for model validation.ResultsSUVmax, MTV, TLG, and MTRasym (3.5 ppm) were higher and D and f were lower in PD-L1 positive NSCLC than in PD-L1 negative NSCLC (all P<0.05). Logistic analysis showed that the combination of MTRasym (3.5 ppm), D, and SUVmax had the strongest predictive value for the differentiation of PD-L1 positive and PD-L1 negative NSCLC [AUC, 0.946; 95% confidence interval (CI): 0.869–0.985; sensitivity, 85.29%; specificity, 91.67%; P all <0.001]. The verification model showed the combination of MTRasym (3.5 ppm), D, and SUVmax had the strongest predictive value, and its ROC curve and calibration curve showed good accuracy (AUC, 0.919, 95% CI: 0.891–0.937) and consistency.ConclusionsMulti-parametric 18F-FDG PET/MRI is beneficial for the non-invasive assessment of PD-L1 status in NSCLC patients, and the combination of SUVmax, D, and MTRasym (3.5 ppm) may serve as a prognostic biomarker to guide immunotherapy.

Differentiating Pyogenic Brain Abscesses and Tuberculous using Magnetization Transfer MR Imaging and in Vivo Proton MR Spectroscopy

Objective: To find whether in vivo proton MR spectroscopy and magnetization transfer (MT) MR imaging can be used to differentiate between tuberculous brain abscess and pyogenic brain abscess. Study Design: Retrospective Place and duration: Radiology Department of Ibn_e_Sina Hospital Multan from January 2021 to January 2022. Methodology: The study included 15 subjects with brain abscesses who underwent in vivo MR spectroscopy, MT MR imaging and conventional MR imaging. Those with other systemic diseases were excluded. These techniques were also performed on 10 sex and age-matched control subjects for comparing MT ratios in normal and diseased parenchymal locations. 13 tuberculous abscesses were found in 4 patients, and 20 pyogenic abscesses were found in 11 patients. MT MR imaging and in vivo MR spectroscopy were used to evaluate suspected brain abscesses. Results: The mean MT ratio of the pyogenic brain abscesses was 25.55±1.60.MR spectroscopy showed that in pyogenic abscesses level of amino acids (valine, isoleucine, leucine) was 0.8 ppm and lipid and lactate was 1.2 ppm. Additionally, acetate, 1.91 ppm; glycine, 3.55 ppm; succinate,2.40 ppm and alanine, 1.47 pm were also seen. Four patients had 13 tuberculous abscesses. The mean MT ratio obtained from tuberculous abscesses was 19.87±1.54, which was significantly lower compared to the cortical grey matter, deep grey matter, white matter and pyogenic abscess (p&lt;.001). Conclusion: MT ratios in tuberculous brain abscesses were lower than in pyogenic abscesses. In vivo, MR spectroscopy in pyogenic abscesses did not show amino acids. Tuberculous brain abscess can be differentiated from the pyogenic abscess by using both in vivo MR spectroscopy and MT MR imaging. Keywords: Pyogenic brain abscess, tuberculous brain abscess, MR spectroscopy

MRI Detection of Hepatic N-Acetylcysteine Uptake in Mice.

This proof-of-concept study looked at the feasibility of using a thiol–water proton exchange (i.e., CEST) MRI contrast to detect in vivo hepatic N-acetylcysteine (NAC) uptake. The feasibility of detecting NAC-induced glutathione (GSH) biosynthesis using CEST MRI was also investigated. The detectability of the GSH amide and NAC thiol CEST effect at B0 = 7 T was determined in phantom experiments and simulations. C57BL/6 mice were injected intravenously (IV) with 50 g L−1 NAC in PBS (pH 7) during MRI acquisition. The dynamic magnetisation transfer ratio (MTR) and partial Z-spectral data were generated from the acquisition of measurements of the upfield NAC thiol and downfield GSH amide CEST effects in the liver. The 1H-NMR spectroscopy on aqueous mouse liver extracts, post-NAC-injection, was performed to verify hepatic NAC uptake. The dynamic MTR and partial Z-spectral data revealed a significant attenuation of the mouse liver MR signal when a saturation pulse was applied at −2.7 ppm (i.e., NAC thiol proton resonance) after the IV injection of the NAC solution. The 1H-NMR data revealed the presence of hepatic NAC, which coincided strongly with the increased upfield MTR in the dynamic CEST data, providing strong evidence that hepatic NAC uptake was detected. However, this MTR enhancement was attributed to a combination of NAC thiol CEST and some other upfield MT-generating mechanism(s) to be identified in future studies. The detection of hepatic GSH via its amide CEST MRI contrast was inconclusive based on the current results.

Utility of Diffusion and Magnetization Transfer MRI in Cervical Spondylotic Myelopathy: A Pilot Study.

Diffusion tensor imaging (DTI) and magnetization transfer (MT) magnetic resonance imaging (MRI) can help detect spinal cord pathology, and tract-specific analysis of their parameters, such as fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), radial diffusivity (RD) and MT ratio (MTR), can give microstructural information. We performed the tract-based acquisition of MR parameters of three major motor tracts: the lateral corticospinal (CS), rubrospinal (RuS) tract, and lateral reticulospinal (RS) tract as well as two major sensory tracts, i.e., the fasciculus cuneatus (FC) and spinal lemniscus, to detect pathologic change and find correlations with clinical items. MR parameters were extracted for each tract at three levels: the most compressed lesion level and above and below the lesion. We compared the MR parameters of eight cervical spondylotic myelopathy patients and 12 normal controls and analyzed the correlation between clinical evaluation items and MR parameters in patients. RuS and lateral RS showed worse DTI parameters at the lesion level in patients compared to the controls. Worse DTI parameters in those tracts were correlated with weaker power grasp at the lesion level. FC and lateral CS showed a correlation between higher RD and lower FA and MTR with a weaker lateral pinch below the lesion level.

139. Quantitative microstructural MRI accurately predicts the likelihood of patients with degenerative cervical myelopathy requiring surgical intervention

<h3>BACKGROUND CONTEXT</h3> The definitive management of degenerative cervical myelopathy (DCM) is surgical decompression in moderate to severe cases. The evidence for early surgical intervention in mild DCM patients is less definitive and therefore, current guidelines are less clear on the relative merits of operative vs nonoperative intervention in this group of patients. According to the best available evidence, anywhere from 20%-62% of patients with mild DCM will deteriorate within 6 years; however, there is no reliable way to predict such a deterioration. However, advances in microstructural MRI may afford a novel approach to address this knowledge gap since these imaging techniques allow one to assess pathological changes such as demyelination, scarring and axonal/neuronal loss. <h3>PURPOSE</h3> Using prospectively collected data, we investigate whether quantitative MRI (qMRI) metrics can predict which patients with DCM are likely to deteriorate clinically and require surgery within one year of presentation. <h3>STUDY DESIGN/SETTING</h3> Prospective cohort study. <h3>PATIENT SAMPLE</h3> This study included 58 DCM patients (33 mild, 15 moderate and 10 severe). <h3>OUTCOME MEASURES</h3> Quantitative MRI metrics and mJOA. <h3>METHODS</h3> Data were stratified into patients who required surgery within one year of follow-up and those who remained stable and continued in the nonoperative group. MRI Acquisition and Image Processing: All patients underwent a multiparametric qMRI scan protocol including diffusion tensor (DTI), magnetization transfer (MT) and T2* weighted imaging at the initial visit. Quantitative metrics including cross sectional area (CSA), fractional anisotropy (FA), magnetization transfer ratio (MTR), and T2* white matter to gray matter ratio (T2*WI WM/GM) were measured in the cervical spine at the rostral, caudal and most compressed levels (MCL). Statistical analysis multivariable logistic regression was performed using baseline FA, MTR and T2*WI WM/GM in the rostral spine and CSA at the MCL as predictor variables. Surgical decompression at one year was used as the dependent variable. Model discrimination and reliability were measured using c-index and Brier's score respectively. Validation and calibration were performed using bootstrap method with 100 repetitions. <h3>RESULTS</h3> A total of 33 mild (mJOA 15-17), 15 moderate (mJOA 12-14) and 10 severe (mJOA 0-11) DCM patients were included in the study. Twenty-eight patients had undergone surgical decompresion at One-year follow-up, whereas the other 28 remained in nonoperative managment. Baseline qMRI was able to identify patients requiring surgery, with an accuracy of 81.6% (AUC or c-index). The model showed good reliability with a Brier score of 0.18 and Somers' Dxy rank correlation of 0.63. Calibration using bootstrap method showed overall good predictive ability with slight over prediction at higher observed probability of surgery. <h3>CONCLUSIONS</h3> Baseline quantitative MRI is able to accurately predict the likelihood of deterioration and surgical intervention in DCM patients. It can potentially play an important role in screening patient populations for surgical candidates or those who are at high risk of deterioration. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

The feasibility of amide proton transfer imaging at 3 T for bladder cancer: a preliminary study

To investigate the optimal amide proton transfer (APT) imaging parameters for bladder cancer (BCa), the influence of different protein concentrations and pH values on APT imaging, and to establish the reliability of APT imaging in healthy volunteers and patients with BCa. The optimal APT imaging parameters for BCa were experimentally optimised using cross-linked bovine serum albumin (BSA) phantoms. BSA phantoms were scanned with different values for the saturation power, saturation duration and number of excitations. Meanwhile, BSA phantoms containing different protein concentrations and solutions of different pH levels were scanned. The interobserver agreement of the asymmetric magnetisation transfer ratio (MTRasym) was assessed in 11 healthy volunteers and 18 patients with BCa. The optimal scanning scheme consisted of 1 excitation, a saturation power of 2 μT, and a saturation time of 2 s. The APT signal intensity increased as the protein concentration increased and as the pH decreased. The MTRasym showed good concordance for all subjects. The MTRasym of BCa tissue was significantly higher (1.81±0.71) than that of bladder wall in healthy volunteers (0.34±0.12) and normal bladder wall in patients with BCa (0.31±0.11; p<0.001). There was no significant difference between the bladder wall of healthy volunteers and the normal bladder wall of patients with BCa. APT imaging showed potential value for application in BCa.

Preliminary Application of Magnetization Transfer Imaging in the Study of Normal Uterus and Uterine Lesions.

PurposeThe aim of this study is to evaluate the utility of magnetization transfer (MT) imaging in the study of normal uterus and common uterine lesions.MethodsThis prospective study enrolled 160 consecutive patients with suspected uterine lesions. MT ratio (MTR) map was obtained by pelvic MT imaging on a 3.0T MRI scanner. Patients confirmed by pathology were divided into microscopic lesion group and lesion group, according to whether the maximum diameter of the lesion was less than 5 mm. After evaluating and eliminating patients with poor image quality by a three-point Likert scale, MTR values of lesions and normal endometrium, myometrium, and cervix were independently measured on the MTR map by two radiologists. Inter-reader agreement was evaluated. MTR values were compared among different uterine lesions and normal uterine structures using the Mann–Whitney U test with Bonferroni correction. Receiver operating characteristic curve was performed. The correlations between age and MTR values were explored by Pearson correlation analyses.ResultsA total of 96 patients with 121 uterine lesions in the lesion group and 41 patients in the microscopic lesion group were measured. The MTR values among normal endometrium, myometrium, and cervix were statistical significant differences (P < 0.05). There were significant differences between endometrial cancer and normal endometrium and between cervical cancer and normal cervix (both P ≤ 0.001). Area under the curve (AUC) for diagnosing endometrial and cervical cancer were 0.73 and 0.86. Myometrial lesions had significantly higher MTR values than endometrial lesions and cervical cancer (both P < 0.001), and the AUC for differentiating myometrial lesions from them were 0.89 and 0.94. MTR values of endometrial cancer were significantly higher than those of cervical cancer (P = 0.02). There was a critical correlation between age and MTR values in endometrial cancer (r = 0.81, P = 0.04).ConclusionsMTR values showed significant differences among normal uterine structures. It was valuable for diagnosing and differentiating uterine cancer. MTR values could differentiate myometrial lesions from endometrial or cervical lesions.

Texture analysis in brain T2 and diffusion MRI differentiates histology-verified grey and white matter pathology types in multiple sclerosis

BackgroundMultiple sclerosis (MS) is a co mplex disease of the central nervous system involving several types of brain pathology that are difficult to characterize using conventional imaging methods. New methodWe originated novel texture analysis and machine learning approaches for classifying MS pathology subtypes as compared with 2 common advanced MRI measures: magnetization transfer ratio (MTR) and fractional anisotropy (FA). Texture analysis used an optimized grey level co-occurrence matrix method with histology-informed 7T T2-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) from 15 MS and 12 control brain specimens. DTI analysis took an innovative approach that assessed the texture across diffusion directions upsampled from 30 to 90. Tissue types included de- and re-myelinated lesions and normal-appearing areas in both grey and white matter, and diffusely abnormal white matter. Data analyses were stepwise, including: (1) group-wise classification using random forest algorithms based on all or individual imaging parameters; (2) parameter importance ranking; and (3) pairwise analysis using top-ranked features. ResultsTexture analysis performed better than MTR and FA, with T2 texture performed the best. T2 texture measures ranked the highest in classifying most grey and white matter tissue types, including de- versus re-myelinated lesions and among grey matter lesion subtypes (accuracy=0.86–0.59; kappa=0.60–0.41). Diffusion texture best differentiated normal appearing and control white matter. Comparison with existing methodsThere is no established method in imaging for differentiating MS pathology subtypes. In combined texture analysis and machine learning studies, there is also no direct evidence comparing conventional with advanced MRI measures for assessing MS pathology. Further, this study is unique in conducting innovative texture analysis with DTI following data-augmentation using robust methods. ConclusionsT2 and diffusion MRI texture analysis integrated with machine learning may be valuable approaches for characterizing MS pathology.