Diffusion Weighted Imaging Metrics Research Articles

Test-retest repeatability and reproducibility of ADC measures by breast DWI: Results from the ACRIN 6698 trial.

Quantitative diffusion-weighted imaging (DWI) MRI is a promising technique for cancer characterization and treatment monitoring. Knowledge of the reproducibility of DWI metrics in breast tumors is necessary to apply DWI as a clinical biomarker. To evaluate the repeatability and reproducibility of breast tumor apparent diffusion coefficient (ADC) in a multi-institution clinical trial setting, using standardized DWI protocols and quality assurance (QA) procedures. Prospective. In all, 89 women from nine institutions undergoing neoadjuvant chemotherapy for invasive breast cancer. DWI was acquired before and after patient repositioning using a four b-value, single-shot echo-planar sequence at 1.5T or 3.0T. A QA procedure by trained operators assessed artifacts, fat suppression, and signal-to-noise ratio, and determine study analyzability. Mean tumor ADC was measured via manual segmentation of the multislice tumor region referencing DWI and contrast-enhanced images. Twenty cases were evaluated multiple times to assess intra- and interoperator variability. Segmentation similarity was assessed via the Sørenson-Dice similarity coefficient. Repeatability and reproducibility were evaluated using within-subject coefficient of variation (wCV), intraclass correlation coefficient (ICC), agreement index (AI), and repeatability coefficient (RC). Correlations were measured by Pearson's correlation coefficients. In all, 71 cases (80%) passed QA evaluation: 44 at 1.5T, 27 at 3.0T; 60 pretreatment, 11 after 3 weeks of taxane-based treatment. ADC repeatability was excellent: wCV = 4.8% (95% confidence interval [CI] 4.0, 5.7%), ICC = 0.97 (95% CI 0.95, 0.98), AI = 0.83 (95% CI 0.76, 0.87), and RC = 0.16 * 10-3 mm2 /sec (95% CI 0.13, 0.19). The results were similar across field strengths and timepoint subgroups. Reproducibility was excellent: interreader ICC = 0.92 (95% CI 0.80, 0.97) and intrareader ICC = 0.91 (95% CI 0.78, 0.96). Breast tumor ADC can be measured with excellent repeatability and reproducibility in a multi-institution setting using a standardized protocol and QA procedure. Improvements to DWI image quality could reduce loss of data in clinical trials. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1617-1628.

Axonal conduction in multiple sclerosis: A combined magnetic resonance imaging and electrophysiological study of the medial longitudinal fasciculus

Objective: The objective of this paper is to inform the pathophysiology of medial longitudinal fasciculus (MLF) axonal dysfunction in patients with internuclear ophthalmoplegia (INO) due to multiple sclerosis (MS), and develop a composite structural-functional biomarker of axonal and myelin integrity in this tract. Methods: Eighteen patients with definite MS and clinically suspected INO underwent electrical vestibular stimulation and search-coil eye movement recording. Components of the electrically evoked vestibulo-ocular reflex (eVOR) were analyzed to probe the latency and fidelity of MLF axonal conduction. The MLF and T2-visible brainstem lesions were defined by high-resolution MRI. White matter integrity was determined by diffusion-weighted imaging metrics. Results: eVOR onset latency was positively correlated with MLF lesion length (left: r = 0.66, p = 0.004; right: r = 0.75, p = 0.001). The mean conduction velocity (±SD) within MLF lesions was estimated at 2.72 (±0.87) m/s. eVOR onset latency correlated with normalized axial diffusivity (r = 0.66, p < 0.001) and fractional anisotropy (r = 0.44, p = 0.02) after exclusion of cases with ipsilateral vestibular root entry zone lesions. Conclusions: Axonal conduction velocity through lesions involving the MLF was reduced below levels predicted for natively myelinated and remyelinated axons. Composite in vivo biomarkers enable delineation of axonal from myelin processes and may provide a crucial role in assessing efficacy of novel reparative therapies in MS.

66.: Medial longitudinal fasciculus: A window on axonal function in multiple sclerosis

This study aims to inform the pathophysiology of axonal dysfunction in the medial longitudinal fasciculus (MLF) in patients with internuclear ophthalmoplegia (INO) in multiple sclerosis (MS), and develop a composite functional-structural biomarker that indirectly distinguishes demyelination from remyelination in this tract. Eighteen patients with definite MS and clinically suspected INO underwent electrical vestibular stimulation and search-coil eye movement recording. Components of the electrically evoked vestibulo-ocular reflex (eVOR) were analyzed to probe the latency and fidelity of MLF axonal conduction. Using a semi-automated technique, the MLF and T2-visible brainstem lesions involving the central vestibular pathways were defined by high-resolution MRI. White matter integrity was determined by diffusion-weighted imaging metrics. INO was associated with a T2-visible lesion within the MLF in all cases. Vestibular root entry zone (VREZ) lesions were observed in five patients (three bilateral, two unilateral). eVOR onset latency was positively correlated with MLF lesion length (left: r = .66, p = .004; right: r = .75, p = .001). Mathematical modelling estimated mean conduction velocity (± standard deviation) within MLF lesions of 2.72 (± 0.87) m/s. eVOR onset latency correlated with normalized axial diffusivity (r = .66, p

Interstitial fluid pressure correlates with intravoxel incoherent motion imaging metrics in a mouse mammary carcinoma model

The effective delivery of a therapeutic drug to the core of a tumor is often impeded by physiological barriers, such as the interstitial fluid pressure (IFP). There are a number of therapies that can decrease IFP and induce tumor vascular normalization. However, a lack of a noninvasive means to measure IFP hinders the utilization of such a window of opportunity for the maximization of the treatment response. Thus, the purpose of this study was to investigate the feasibility of using intravoxel incoherent motion (IVIM) diffusion parameters as noninvasive imaging biomarkers for IFP. Mice bearing the 4T1 mammary carcinoma model were studied using diffusion-weighted imaging (DWI), immediately followed by wick-in-needle IFP measurement. Voxelwise analysis was conducted with a conventional monoexponential diffusion model, as well as a biexponential model taking IVIM into account. There was no significant correlation of IFP with either the median apparent diffusion coefficient from the monoexponential model (r = 0.11, p = 0.78) or the median tissue diffusivity from the biexponential model (r = 0.30, p = 0.44). However, IFP was correlated with the median pseudo-diffusivity (D(p)) of apparent vascular voxels (r = 0.76, p = 0.02) and with the median product of the perfusion fraction and pseudo-diffusivity (f(p)D(p)) of apparent vascular voxels (r = 0.77, p = 0.02). Although the effect of IVIM in tumors has been reported previously, to our knowledge, this study represents the first direct comparison of IVIM metrics with IFP, with the results supporting the feasibility of the use of IVIM DWI metrics as noninvasive biomarkers for tumor IFP.

Diffusion-Weighted Imaging and Cognition in the Leukoariosis and Disability in the Elderly Study

The mechanisms by which leukoariosis impacts on clinical and cognitive functions are not yet fully understood. We hypothesized that ultrastructural abnormalities of the normal-appearing brain tissue (NABT) assessed by diffusion-weighted imaging played a major and independent role. In addition to a comprehensive clinical, neuropsychologic, and imaging work-up, diffusion-weighted imaging was performed in 340 participants of the multicenter leukoariosis and disability study examining the impact of white matter hyperintensities (WMH) on 65- to 85-year old individuals without previous disability. WMH severity was rated according to the Fazekas score. Multivariate regression analysis served to assess correlations of histogram metrics of the apparent diffusion coefficient (ADC) of whole-brain tissue, NABT, and of the mean ADC of WMH with cognitive functions. Increasing WMH scores were associated with a higher frequency of hypertension, a greater WMH volume, more brain atrophy, worse overall cognitive performance, and changes in ADC. We found strong associations between the peak height of the ADC histogram of whole-brain tissue and NABT with memory performance, executive dysfunction, and speed, which remained after adjustment for WMH lesion volume and brain atrophy and were consistent among centers. No such association was seen with the mean ADC of WMH. Ultrastructural abnormalities of NABT increase with WMH severity and have a strong and independent effect on cognitive functions, whereas diffusion-weighted imaging metrics within WMH have no direct impact. This should be considered when defining outcome measures for trials that attempt to ameliorate the consequences of WMH progression.

Differentiating multiple sclerosis from other causes of demyelination using diffusion weighted imaging of the corpus callosum

To compare diffusion weighted imaging metrics in gray and white matter brain regions of patients diagnosed with multiple sclerosis (MS) to those diagnosed with secondary demyelinating diseases such as neurosarcoid and acute disseminated encephalomyelitis (ADEM). Diffusion weighted scans were performed and apparent diffusion coefficients of 12 regions of interest were determined in 30 MS patients, 21 neurosarcoid patients, and 4 ADEM patients. Mean apparent diffusion coefficients were significantly higher in MS patients than in non-MS patients in 6 of 6 of the corpus callosal regions assessed but not in any of the non-callosal white or gray matter regions assessed. Elevated apparent diffusion coefficients within the corpus callosum on diffusion weighted imaging may potentially help differentiate between patients with MS and patients with other diseases affecting the central nervous system white matter.