Quantitative Magnetic Resonance Imaging Biomarkers Research Articles

Quantitative MRI Biomarkers Measure Changes in Targeted Brain Areas in Patients With Obesity.

Obesity is accompanied by damages to several tissues, including the brain. Pathological data and animal models have demonstrated an increased inflammatory reaction in hypothalamus and hippocampus. We tested whether we could observe such pathological modifications in vivo through quantitative magnetic resonance imaging (MRI) metrics. This prospective study was conducted between May 2019 and November 2022. The study was conducted in the Specialized Center for the Care of Obesity in a French University Hospital. Twenty-seven patients with obesity and 23 age and gender-paired normal-weight controls were prospectively recruited. All participants were examined using brain MRI. Anthropometric and biological data, eating behavior, anxiety, depression, and memory performance were assessed in both groups. The main outcome measure was brain MRI with the following parametric maps: quantitative susceptibility mapping (QSM), mean diffusivity (MD), fractional anisotropy (FA), magnetization transfer ratio map, and T2 relaxivity map. In the hypothalamus, patients with obesity had higher FA and lower QSM than normal-weight controls. In the hippocampus, patients with obesity had higher FA and lower MD. There was no correlation between imaging biomarkers and eating behavior or anxiety. Our findings are consistent with the presence of neuroinflammation in brain regions involved in food intake. In vivo brain biomarkers from quantitative MRI appear to provide an incremental information for the assessment of brain damages in patients with obesity.

Repeatability of Quantitative Magnetic Resonance Imaging Biomarkers in the Tibia Bone Marrow of a Murine Myelofibrosis Model.

Quantitative MRI biomarkers are sought to replace painful and invasive sequential bone-marrow biopsies routinely used for myelofibrosis (MF) cancer monitoring and treatment assessment. Repeatability of MRI-based quantitative imaging biomarker (QIB) measurements was investigated for apparent diffusion coefficient (ADC), proton density fat fraction (PDFF), and magnetization transfer ratio (MTR) in a JAK2 V617F hematopoietic transplant model of MF. Repeatability coefficients (RCs) were determined for three defined tibia bone-marrow sections (2-9 mm; 10-12 mm; and 12.5-13.5 mm from the knee joint) across 15 diseased mice from 20-37 test-retest pairs. Scans were performed on consecutive days every two weeks for a period of 10 weeks starting 3-4 weeks after transplant. The mean RC with (95% confidence interval (CI)) for these sections, respectively, were for ADC: 0.037 (0.031, 0.050), 0.087 (0.069, 0.116), and 0.030 (0.022, 0.044) μm2/ms; for PDFF: 1.6 (1.3, 2.0), 15.5 (12.5, 20.2), and 25.5 (12.0, 33.0)%; and for MTR: 0.16 (0.14, 0.19), 0.11 (0.09, 0.15), and 0.09 (0.08, 0.15). Change-trend analysis of these QIBs identified a dynamic section within the mid-tibial bone marrow in which confident changes (exceeding RC) could be observed after a four-week interval between scans across all measured MRI-based QIBs. Our results demonstrate the capability to derive quantitative imaging metrics from mouse tibia bone marrow for monitoring significant longitudinal MF changes.

The emerging potential of quantitative MRI biomarkers for the early prediction of brain metastasis response after stereotactic radiosurgery: a scoping review.

At present, the simple prognostic models based on clinical information for predicting the treatment outcomes of brain metastases (BMs) are subjective and delayed. Thus, we performed this systematic review of multiple studies to assess the potential of quantitative magnetic resonance imaging (MRI) biomarkers for the early prediction of treatment outcomes of brain metastases with stereotactic radiosurgery (SRS). We systematically searched the PubMed, Embase, Cochrane, Web of Science, and Clinical Trials.gov databases for articles published between February 1, 1991, and April 11, 2022, with no language restrictions. We included studies involving patients with BMs receiving SRS; the included patients were required to have definite pathology of a primary tumor and complete imaging data (pre- and post-SRS). We excluded the articles that included patients who had undergone previous surgery and those that did not include regular follow-up or corresponding MRI scans. We identified 2,162 studies, of which 26 were included in our analysis, involving a total of 1,362 participants. All 26 studies explored the relevant MRI parameters to predict the prognosis of patients with BMs who received SRS. The outcomes were generalized according to the relationships between the anatomical/morphological, microstructural, vascular, and metabolic changes and SRS. Generally, with traditional MRI, there are several quantitative prognostic models based on preradiosurgical radiomics that predict the outcome of SRS treatment in local BM control. With the implementation of advanced MRI, the relative apparent diffusion coefficient (ADC), perfusion fraction (f), relative cerebral blood volume (rCBV), relative regional cerebral blood flow (rrCBF), interstitial fluid pressure (IFP), quadratic of time-dependent leakage (Ktrans 2), extracellular extravascular volume (ve), choline/creatine (Cho/Cr), nuclear Overhauser effect (NOE) peak, and intraextracellular water exchange rate constant (kIE ) were confirmed to be indicative of the therapeutic effect of SRS for BMs. Quantitative MRI biomarkers extracted from traditional or advanced MRI at different time points, which can represent the anatomical/morphological, microstructural, vascular, and metabolic changes, respectively, have been proposed as promising markers for the early prediction of SRS response in those with BMs. There are some limitations in this review, including the risk of selection bias, the limited number of study objects, the incomparability of the total data, and the subjectivity of the review process.

A preliminary diagnostic accuracy study of quantitative MRI biomarkers for differentiating parotid tumor types.

Differentiating among the different types of parotid tumors on imaging is useful for guiding clinical disposition, which ultimately may lead to surgical management. The goal of this study was to determine whether quantitative T2 signal characteristics and morphologic features on magnetic resonance imaging (MRI) can serve as predictive biomarkers for distinguishing between tumor types. A retrospective review of T2-weighted MRIs in patients with pathology-proven parotid tumors was performed. Quantitative T2 maps and surface regularity measurements of the tumors were obtained via semi-automated regions of interest (ROI). Linear Discriminant Analysis was used to populate the receiver operating characteristics (ROCs) curves for these variables. A P value of <0.05 was considered to be significant. A total of 35 tumors (21 benign and 14 malignant neoplasms) were included in this analysis. For differentiating the benign versus malignant classes of parotid tumors, T2 signal and surface regularity combined yielded an area under the curve of 0.62 (P value: 0.2) through the ROC analysis. However, for the pleomorphic adenomas versus other types of parotid tumors, using both T2 signal and surface regularity yielded an area under the curve of 0.81 (P value: 0.007) through the ROC analysis. T2 signal and surface regularity combined can significantly differentiate pleomorphic adenomas from other types of parotid tumors and can potentially be used as a predictive imaging biomarker.

Quantitative magnetic resonance imaging biomarkers for cortical pathology in multiple sclerosis at 7 T.

Substantial cortical gray matter tissue damage, which correlates with clinical disease severity, has been revealed in multiple sclerosis (MS) using advanced magnetic resonance imaging (MRI) methods at 3T and the use of ultra-high field, as well as in histopathology studies. While clinical assessment mainly focuses on lesions using - and -weighted MRI, quantitative MRI (qMRI) methods are capable of uncovering subtle microstructural changes. The aim of this ultra-high field study is to extract possible future MR biomarkers for the quantitative evaluation of regional cortical pathology. Because of their sensitivity to iron, myelin, and in part specifically to cortical demyelination, , , , and susceptibility mapping were performed including two novel susceptibility markers; in addition, cortical thickness as well as the volumes of 34 cortical regions were computed. Data were acquired in 20 patients and 16 age- and sex-matched healthy controls. In 18 cortical regions, large to very large effect sizes (Cohen's d ≥1) and statistically significant differences in qMRI values between patients and controls were revealed compared with only four regions when using more standard MR measures, namely, volume and cortical thickness. Moreover, a decrease in all susceptibility contrasts ( , , and values indicates that the role of cortical demyelination might outweigh inflammatory processes in the form of iron accumulation in cortical MS pathology, and might also indicate iron loss. A significant association between susceptibility contrasts as well as of the caudal middle frontal gyrus and disease duration was found (adjusted R2 : 0.602, p= 0.0011). Quantitative MRI parameters might be more sensitive towards regional cortical pathology compared with the use of conventional markers only and therefore may play a role in early detection of tissue damage in MS in the future.

Clinical translation of quantitative magnetic resonance imaging biomarkers – An overview and gap analysis of current practice

PurposeThis overview of the current landscape of quantitative magnetic resonance imaging biomarkers (qMR IBs) aims to support the standardisation of academic IBs to assist their translation to clinical practice. MethodsWe used three complementary approaches to investigate qMR IB use and quality management practices within the UK: 1) a literature search of qMR and quality management terms during 2011–2015 and 2016–2020; 2) a database search for clinical research studies using qMR IBs during 2016–2020; and 3) a survey to ascertain the current availability and quality management practices for clinical MRI scanners and associated equipment at research institutions across the UK. ResultsThe analysis showed increased use of all qMR methods between the periods 2011–2015 and 2016–2020 and diffusion-tensor MRI and volumetry to be popular methods. However, the “translation ratio” of journal articles to clinical research studies was higher for qMR methods that have evidence of clinical translation via a commercial route, such as fat fraction and T2 mapping.The number of journal articles citing quality management terms doubled between the periods 2011–2015 and 2016–2020; although, its proportion relative to all journal articles only increased by 3.0%. The survey suggested that quality assurance (QA) and quality control (QC) of data acquisition procedures are under-reported in the literature and that QA/QC of acquired data/data analysis are under-developed and lack consistency between institutions. ConclusionsWe summarise current attempts to standardise and translate qMR IBs, and conclude by outlining the ideal quality management practices and providing a gap analysis between current practice and a metrological standard.

Emerging Imaging Biomarkers in Crohn Disease.

In this review article, we present the latest developments in quantitative imaging biomarkers based on magnetic resonance imaging (MRI), applied to the diagnosis, assessment of response to therapy, and assessment of prognosis of Crohn disease. We also discuss the biomarkers' limitations and future prospects. We performed a literature search of clinical and translational research in Crohn disease using diffusion-weighted MRI (DWI-MRI), dynamic contrast-enhanced MRI (DCE-MRI), motility MRI, and magnetization transfer MRI, as well as emerging topics such as T1 mapping, radiomics, and artificial intelligence. These techniques are integrated in and combined with qualitative image assessment of magnetic resonance enterography (MRE) examinations. Quantitative MRI biomarkers add value to MRE qualitative assessment, achieving substantial diagnostic performance (area under receiver-operating curve = 0.8-0.95). The studies reviewed show that the combination of multiple MRI sequences in a multiparametric quantitative fashion provides rich information that may help for better diagnosis, assessment of severity, prognostication, and assessment of response to biological treatment. However, the addition of quantitative sequences to MRE examinations has potential drawbacks, including increased scan time and the need for further validation before being used in therapeutic drug trials as well as the clinic.

Magnetic resonance imaging biomarkers in musculoskeletal soft tissue tumors: Review of conventional features and focus on nonmorphologic imaging.

The majority of peripheral musculoskeletal soft tissue masses encountered in routine clinical practice are benign and associated with an excellent prognosis, whereas a small proportion of soft tissue masses are malignant and are associated with higher morbidity and mortality. Owing to the excellent tissue contrast resolution provided, magnetic resonance imaging (MRI) is a primary modality for the diagnostic evaluation of soft tissue masses, particularly for defining the anatomic extent. MRI is also useful for the characterization of soft tissue masses; however, after the exclusion of cysts and lipomas, it is challenging to accurately categorize neoplastic lesions as benign or malignant with conventional anatomic MRI. Quantitative MRI biomarkers obtained with nonconventional pulse sequences are becoming increasingly available, and can improve the accuracy of determining the character of soft tissue masses. In this article we discuss established qualitative and emerging quantitative MRI-based biomarkers available with dynamic contrast-enhanced MRI, diffusion-weighted imaging, and MR spectroscopy and their utility for the characterization of untreated soft tissue masses. Level of Evidence: 5 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:11-27.

Diagnostic performance of quantitative magnetic resonance imaging biomarkers for predicting portal hypertension in children and young adults with autoimmune liver disease.

Primary sclerosing cholangitis, autoimmune hepatitis and autoimmune sclerosing cholangitis are forms of chronic, progressive autoimmune liver disease (AILD) that can affect the pediatric population. To determine whether quantitative MRI- and laboratory-based biomarkers are associated with conventional imaging findings of portal hypertension (radiologic portal hypertension) in children and young adults with AILD. Forty-four patients with AILD enrolled in an institutional registry underwent a research abdominal MRI examination at 1.5 tesla(T). Five quantitative MRI techniques were performed: liver MR elastography, spleen MR elastography, liver iron-corrected T1 mapping, liver T2 mapping, and liver diffusion-weighted imaging (DWI, quantified as apparent diffusion coefficients). Two anatomical sequences were used to document splenomegaly, varices and ascites. We calculated aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores - laboratory-based biomarkers of liver fibrosis. We used receiver operating characteristic (ROC) curve analyses to establish the diagnostic performance of quantitative MRI and laboratory biomarkers for indicating the presence of radiologic portal hypertension. Twenty-three (52%) patients were male; mean age was 15.2±4.0years. Thirteen (30%) patients had radiologic portal hypertension. Liver and spleen stiffness demonstrated the greatest diagnostic performance for indicating the presence of portal hypertension (area-under-the-ROC-curve [AUROC]=0.98 and 0.96, respectively). The APRI and FIB-4 scores also demonstrated good diagnostic performance (AUROC=0.87 and 0.88, respectively). MRI-derived measures of liver and spleen stiffness as well as laboratory-based APRI and FIB-4 scores are highly associated with imaging findings of portal hypertension in children and young adults with AILD and thus might be useful for predicting portal hypertension impending onset and directing personalized patient management.

Detecting frontotemporal dementia syndromes using MRI biomarkers.

BackgroundDiagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another.MethodsIn this retrospective multicenter cohort study, we included 1213 patients (age 67 ± 9, 48% females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer's disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline. Three MRI atrophy biomarkers were derived from the normalized volumes of automatically segmented cortical regions: 1) the anterior vs. posterior index, 2) the asymmetry index, and 3) the temporal pole left index. We used the following performance metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. To account for the low prevalence of frontotemporal dementia we pursued a high specificity of 95%. Cross-validation was used in assessing the performance. The generalizability was assessed in an independent cohort (n = 200).ResultsThe anterior vs. posterior index performed with an AUC of 83% for differentiation of frontotemporal dementia from all other diagnostic groups (Sensitivity = 59%, Specificity = 95%, positive likelihood ratio = 11.8, negative likelihood ratio = 0.4). The asymmetry index showed highest performance for separation of primary progressive aphasia and behavioral variant frontotemporal dementia (AUC = 85%, Sensitivity = 79%, Specificity = 92%, positive likelihood ratio = 9.9, negative likelihood ratio = 0.2), whereas the temporal pole left index was specific for detection of semantic variant primary progressive aphasia (AUC = 85%, Sensitivity = 82%, Specificity = 80%, positive likelihood ratio = 4.1, negative likelihood ratio = 0.2). The validation cohort provided corresponding results for the anterior vs. posterior index and temporal pole left index.ConclusionThis study presents three quantitative MRI biomarkers, which could provide additional information to the diagnostic assessment and assist clinicians in diagnosing frontotemporal dementia.

Quantitative magnetic resonance imaging biomarkers in oncological clinical trials: Current techniques and standardization challenges

Radiological imaging plays an important role in oncological trials to provide imaging biomarkers for disease staging, stratifying patients, defining dose setting, and evaluating the safety and efficacy of new candidate drugs and innovative treatment. This paper reviews the techniques of most commonly used quantitative magnetic resonance imaging (qMRI) biomarkers (dynamic contrast enhanced, dynamic susceptibility contrast, and diffusion weighted imaging) and their applications in oncological trials. Challenges of incorporating qMRI biomarkers in oncological trials are discussed including understanding biological mechanisms revealed by MRI biomarkers, consideration of rigorous trial design and standardized implementation of qMRI protocols.

Quantitative OCT and MRI biomarkers for the differentiation of cartilage degeneration.

To evaluate the usefulness of quantitative parameters obtained by optical coherence tomography (OCT) and magnetic resonance imaging (MRI) in the comprehensive assessment of human articular cartilage degeneration. Human osteochondral samples of variable degeneration (n = 45) were obtained from total knee replacements and assessed by MRI sequences measuring T1, T1ρ, T2 and T2* relaxivity and by OCT-based quantification of irregularity (OII, optical irregularity index), homogeneity (OHI, optical homogeneity index]) and attenuation (OAI, optical attenuation index]). Samples were also assessed macroscopically (Outerbridge classification) and histologically (Mankin classification) as grade-0 (Mankin scores 0-4)/grade-I (scores 5-8)/grade-II (scores 9-10)/grade-III (score 11-14). After data normalisation, differences between Mankin grades and correlations between imaging parameters were assessed using ANOVA and Tukey's post-hoc test and Spearman's correlation coefficients, respectively. Sensitivities and specificities in the detection of Mankin grade-0 were calculated. Significant degeneration-related increases were found for T2 and OII and decreases for OAI, while T1, T1ρ, T2* or OHI did not reveal significant changes in relation to degeneration. A number of significant correlations between imaging parameters and histological (sub)scores were found, in particular for T2 and OII. Sensitivities and specificities in the detection of Mankin grade-0 were highest for OHI/T1 and OII/T1ρ, respectively. Quantitative OCT and MRI techniques seem to complement each other in the comprehensive assessment of cartilage degeneration. Sufficiently large structural and compositional changes in the extracellular matrix may thus be parameterized and quantified, while the detection of early degeneration remains challenging.

Be it resolved: plain radiography or MRI – which is better in assessing outcome in clinical trials?

Be it resolved: plain radiography or MRI – which is better in assessing outcome in clinical trials?

Cartilage repair surgery: outcome evaluation by using noninvasive cartilage biomarkers based on quantitative MRI techniques?

Background. New quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair.

Emerging quantitative magnetic resonance imaging biomarkers of hepatic steatosis

Emerging quantitative magnetic resonance imaging biomarkers of hepatic steatosis

Potential Quantitative Magnetic Resonance Imaging Biomarkers of Coronary Remodeling in Older Hypertensive Patients

To detect differences in potential magnetic resonance imaging biomarkers of coronary remodeling between older hypertensive patients and healthy controls. Two-dimensional black-blood coronary wall magnetic resonance imaging and 3-dimensional whole-heart coronary magnetic resonance angiography were performed on 130 participants (65-84 years), including 65 hypertensive patients and 65 healthy controls. Coronary segments derived from hypertensive participants had a higher mean coronary wall thickness, a smaller vessel area, a smaller coronary wall area, a smaller lumen area, a lower coronary distensibility index, and a higher percent of the coronary wall occupying the vessel area (PWOV) than those from healthy controls. When the average PWOV was set as an ad hoc cutoff point, coronary segments with a high PWOV had a significantly higher mean wall thickness, a higher maximum wall thickness, a smaller vessel area, a smaller lumen area, a lower coronary distensibility index, and a higher coronary plaque index compared with coronary segments with a low PWOV. Magnetic resonance techniques are able to noninvasively detect significant differences in potential imaging biomarkers of coronary remodeling between older hypertensive patients and healthy controls. The PWOV is a promising remodeling feature for quantitatively evaluating the progression of coronary atherosclerosis.

Damage to the Optic Radiation in Multiple Sclerosis Is Associated With Retinal Injury and Visual Disability

To determine whether damage to the optic radiation (OR) in multiple sclerosis (MS) is associated with optic nerve injury and visual dysfunction. Case-control study. Referral center. Ninety referred patients with MS and 29 healthy volunteers. Magnetic resonance imaging indices along the OR were reconstructed with diffusion tensor tractography. Retinal nerve fiber layer thickness and visual acuity at high and low contrast were measured in a subset of the MS group (n = 36). All tested magnetic resonance imaging indices (fractional anisotropy [FA]; mean, parallel, and perpendicular [lambda( perpendicular)] diffusivity; T2 relaxation time; and magnetization transfer ratio) were significantly abnormal in patients with MS. Mean retinal nerve fiber layer thickness was significantly correlated with FA (r = 0.55; P < .001) and lambda( perpendicular) (r = -0.37; P = .001). The retinal nerve fiber layer thickness in the nasal retinal quadrant was also specifically correlated with FA and lambda( perpendicular) in the synaptically connected contralateral OR. In individuals with less severely damaged optic nerves (mean retinal nerve fiber layer thickness >80 mum), letter acuity scores at 2.5% contrast were correlated with OR-specific FA (r = 0.55; P = .004), lambda( perpendicular) (r = -0.40; P = .04), and magnetization transfer ratio (r = 0.54; P = .01), as well as the fraction of OR volume made up of lesions (r = -0.69; P < .001). Fractional anisotropy and lambda( perpendicular) are potentially useful quantitative magnetic resonance imaging biomarkers of OR-specific damage in MS. Such damage is associated with retinal injury and visual disability.

Quantitative MRI Biomarkers of Cognitive Morbidity in Temporal Lobe Epilepsy

To determine the relation between neuropsychological morbidity, quantitative magnetic resonance imaging (MRI) measures of whole brain structure, and clinical seizure factors reflecting epilepsy cause, course, and treatment. Quantitative MRI measurements of total (whole brain) cerebrospinal fluid (CSF) and gray- and white-matter volumes and clinical seizure features were examined in relation to summary indices of cognitive morbidity in 96 patients with temporal lobe epilepsy. MRI volumes were adjusted for intracranial volume (ICV), and cognitive scores were adjusted for age, education, and gender, based on a sample of 82 healthy controls. Whole-brain volumes (gray, white, and CSF) were abnormal in chronic temporal lobe epilepsy patients compared with controls and were related significantly to neuropsychological morbidity, especially total CSF. Statistical modeling demonstrated that markers of total atrophy (CSF) was the primary mediator of the relation between clinical seizure variables and neuropsychological morbidity. Quantitative measurements of overall brain abnormality (atrophy) in temporal lobe epilepsy are clinically meaningful markers that are associated with increased cognitive morbidity. These biomarkers appear to mediate the adverse effects of some clinical seizure variables on cognition.