non-Gaussian Diffusion Models Research Articles

Feasibility of Diffusion-weighted Imaging (DWI) for Assessing Cerebrospinal Fluid Dynamics: DWI-fluidography in the Brains of Healthy Subjects.

The present study aimed to investigate whether diffusion-weighted imaging (DWI) can qualify and quantify cerebrospinal fluid (CSF) dynamics in the brains of healthy subjects. For this purpose, we developed new DWI-based fluidography and compared the CSF dynamics seen on the fluidography with two apparent diffusion coefficients obtained with different DWI signal models at anatomical spaces filled by CSF. DWI with multiple b values was performed for 10 subjects using a 7T MRI scanner. DWI-fluidography based on the DWI signal variations in different motion probing gradient directions was developed for visualizing the CSF dynamics voxel-by-voxel. DWI signals were measured using an ROI in the representative CSF-filled anatomical spaces in the brain. For the multiple DWI signals, the mono-exponential and kurtosis models were fitted and two kinds of apparent diffusion coefficients (ADCC and ADCK) were estimated in each space using the Gaussian and non-Gaussian diffusion models, respectively. DWI-fluidography could qualitatively represent the features of CSF dynamics in each anatomical space. ADCs indicated that the motions at the foramen of Monro, the cistern of the velum interpositum, the quadrigeminal cistern, the Sylvian cisterns, and the fourth ventricle were more drastic than those at the subarachnoid space and anterior horns of the lateral ventricle. Those results seen in ADCs were identical to the findings on DWI-fluidography. DWI-fluidography based on the features of DWI signals could show differences of CSF dynamics among anatomical spaces.

Accelerating High b-Value Diffusion-Weighted MRI Using a Convolutional Recurrent Neural Network (CRNN-DWI).

To develop a novel convolutional recurrent neural network (CRNN-DWI) and apply it to reconstruct a highly undersampled (up to six-fold) multi-b-value, multi-direction diffusion-weighted imaging (DWI) dataset. A deep neural network that combines a convolutional neural network (CNN) and recurrent neural network (RNN) was first developed by using a set of diffusion images as input. The network was then used to reconstruct a DWI dataset consisting of 14 b-values, each with three diffusion directions. For comparison, the dataset was also reconstructed with zero-padding and 3D-CNN. The experiments were performed with undersampling rates (R) of 4 and 6. Standard image quality metrics (SSIM and PSNR) were employed to provide quantitative assessments of the reconstructed image quality. Additionally, an advanced non-Gaussian diffusion model was employed to fit the reconstructed images from the different approaches, thereby generating a set of diffusion parameter maps. These diffusion parameter maps from the different approaches were then compared using SSIM as a metric. Both the reconstructed diffusion images and diffusion parameter maps from CRNN-DWI were better than those from zero-padding or 3D-CNN. Specifically, the average SSIM and PSNR of CRNN-DWI were 0.750 ± 0.016 and 28.32 ± 0.69 (R = 4), and 0.675 ± 0.023 and 24.16 ± 0.77 (R = 6), respectively, both of which were substantially higher than those of zero-padding or 3D-CNN reconstructions. The diffusion parameter maps from CRNN-DWI also yielded higher SSIM values for R = 4 (>0.8) and for R = 6 (>0.7) than the other two approaches (for R = 4, <0.7, and for R = 6, <0.65). CRNN-DWI is a viable approach for reconstructing highly undersampled DWI data, providing opportunities to reduce the data acquisition burden.

Non-Gaussian model-based diffusion-weighted imaging of oral squamous cell carcinoma: associations with Ki-67 proliferation status.

To investigate possible associations between diffusion-weighted imaging (DWI) parameters derived from a non-Gaussian model fitting and Ki-67 status in patients with oral squamous cell carcinoma (OSCC). Twenty-four patients with newly diagnosed OSCC were prospectively recruited. DWI was performed using six b-values (0-2500). The diffusion-related parameters of kurtosis value (K), kurtosis-corrected diffusion coefficient (DK), diffusion heterogeneity (α), distributed diffusion coefficient (DDC), slow diffusion coefficient (Dslow), and apparent diffusion coefficient (ADC) were calculated from four diffusion fitting models. Ki-67 status was categorized as low (Ki-67 percentage score < 20%), middle (20-50%), or high (> 50%). Kruskal-Wallis tests were performed between each non-Gaussian diffusion model parameters and Ki-67 grade. The Kruskal-Wallis tests revealed that multiple parameters (K, ADC, Dk, DDC and Dslow) showed statistically significant differences between the three levels of Ki-67 status (K: p = 0.020, ADC: p = 0.012, Dk: p = 0.027, DDC: p = 0.007 and Dslow: p = 0.026). Several non-Gaussian diffusion model parameters and ADC values were significantly associated with Ki-67 status and have potential as promising prognostic biomarkers in patients with OSCC.

A comparison study of monoexponential and fractional order calculus diffusion models and 18F-FDG PET in differentiating benign and malignant solitary pulmonary lesions and their pathological types.

ObjectiveTo evaluate the application value of monoexponential, fractional order calculus (FROC) diffusion models and PET imaging to distinguish between benign and malignant solitary pulmonary lesions (SPLs) and malignant SPLs with different pathological types and explore the correlation between each parameter and Ki67 expression.MethodsA total of 112 patients were enrolled in this study. Prior to treatment, all patients underwent a dedicated thoracic 18F-FDG PET/MR examination. Five parameters [including apparent diffusion coefficient (ADC) derived from the monoexponential model; diffusion coefficient (D), a microstructural quantity (μ), and fractional order parameter (β) derived from the FROC model and maximum standardized uptake value (SUVmax) derived from PET] were compared between benign and malignant SPLs and different pathological types of malignant SPLs. Independent sample t test, Mann-Whitney U test, DeLong test and receiver operating characteristic (ROC) curve analysis were used for statistical evaluation. Pearson correlation analysis was used to calculate the correlations between Ki-67 and ADC, D, μ, β, and SUVmax.ResultsThe ADC and D values were significantly higher and the μ and SUVmax values were significantly lower in the benign group [1.57 (1.37, 2.05) μm2/ms, 1.59 (1.52, 1.72) μm2/ms, 5.06 (3.76, 5.66) μm, 5.15 ± 2.60] than in the malignant group [1.32 (1.03, 1.51) μm2/ms, 1.43 (1.29, 1.52) μm2/ms, 7.06 (5.87, 9.45) μm, 9.85 ± 4.95]. The ADC, D and β values were significantly lower and the μ and SUVmax values were significantly higher in the squamous cell carcinoma (SCC) group [1.29 (0.66, 1.42) μm2/ms, 1.32 (1.02, 1.42) μm2/ms, 0.63 ± 0.10, 9.40 (7.76, 15.38) μm, 11.70 ± 5.98] than in the adenocarcinoma (AC) group [1.40 (1.28, 1.67) μm2/ms, 1.52 (1.44, 1.64) μm2/ms, 0.70 ± 0.10, 5.99 (4.54, 6.87) μm, 8.76 ± 4.18]. ROC curve analysis showed that for a single parameter, μ exhibited the best AUC value in discriminating between benign and malignant SPLs groups and AC and SCC groups (AUC = 0.824 and 0.911, respectively). Importantly, the combination of monoexponential, FROC models and PET imaging can further improve diagnostic performance (AUC = 0.872 and 0.922, respectively). The Pearson correlation analysis showed that Ki67 was positively correlated with μ value and negatively correlated with ADC and D values (r = 0.402, -0.346, -0.450, respectively).ConclusionThe parameters D and μ derived from the FROC model were superior to ADC and SUVmax in distinguishing benign from malignant SPLs and adenocarcinoma from squamous cell carcinoma, in addition, the combination of multiple parameters can further improve diagnostic performance. The non-Gaussian FROC diffusion model is expected to become a noninvasive quantitative imaging technique for identifying SPLs.

The strength of corticomotoneuronal drive underlies ALS split phenotypes and reflects early upper motor neuron dysfunction.

BackgroundSplit phenotypes, (split hand, elbow, leg, and foot), are probably unique to ALS, and are characterized by having a shared peripheral input of both affected and unaffected muscles. This implies an anatomical origin rostral to the spinal cord, primarily within the cerebral cortex. Therefore, split phenotypes are a potential marker of ALS upper motor neuron pathology. However, to date, reports documenting upper motor neuron dysfunction in split phenotypes have been limited to using transcranial magnetic stimulation and cortical threshold tracking techniques. Here, we consider several other potential methodologies that could confirm a primary upper motor neuron pathology in split phenotypes.MethodsWe review the potential of: 1. measuring the compound excitatory post‐synaptic potential recorded from a single activated motor unit, 2. cortical‐muscular coherence, and 3. new advanced modalities of neuroimaging (high‐resolution imaging protocols, ultra‐high field MRI platforms [7T], and novel Non‐Gaussian diffusion models).ConclusionsWe propose that muscles involved in split phenotypes are those functionally involved in the human motor repertoire used particularly in complex activities. Their anterior horn cells receive the strongest corticomotoneuronal input. This is also true of the weakest muscles that are the earliest to be affected in ALS. Descriptions of split hand in non‐ALS cases and proposals that peripheral nerve or muscle dysfunction may be causative are contentious. Only a few carefully controlled cases of each form of split phenotype, using upper motor neuron directed methodologies, are necessary to prove our postulate.

The predictive value of DKI in breast cancer: Does tumour subtype affect pathological response evaluations?

PurposeTo explore the differences in quantitative parameters based on diffusion weighted imaging (DWI) and diffusion kurtosis imaging (DKI) between different immunohistochemical indicator statuses and their predictive value for neoadjuvant chemotherapy (NAC) among different phenotypes of breast cancer. MethodsEighty-one breast cancer patients who underwent NAC were enrolled in this retrospective study. Correlations between diffusion parameters and immunohistochemical indicators were determined using Spearman's test, and receiver operating characteristic (ROC) curves were constructed to assess the apparent diffusion coefficient (ADC), mean diffusivity (MD), and mean kurtosis (MK) in predicting the pathologic complete response (PCR). ResultsCorrelations were observed between MK values and hormone receptor (HR) expression (oestrogen receptor (ER): r = 0.315 and progesterone receptor (PR): r = 0.268). The parameters ADC(0,1000), MK, and MD all showed correlations with Ki67 expression (r = 0.276, 0.316 and − 0.224, respectively). ER and Ki67 expression and the parameters MD and MK were significantly different between the PCR and non-PCR groups (AUC = 0.783, 0.688, 0.649 and 0.684, respectively). After splitting patients into subgroups, no significant differences were observed between the PCR and non-PCR groups with human epidermal growth factor receptor 2 (HER2) + and triple-negative (TN) breast cancer. However, we were surprised to find that ADC(0, 1000), MD, and MK were significantly different between different remission groups with HR+/HER2+ subtypes, and the AUCs of each parameter reached 0.794, 0.825, and 0.712, respectively. ConclusionMK was correlated with HR expression. ADC(0, 1000) and DKI were correlated with Ki67 expression. ADC(0, 1000) and the non-Gaussian diffusion model are suitable for predicting PCR in patients with HR+/HER2+ breast cancer before NAC.

Diffusion and quantification of diffusion of prostate cancer.

For assessing a cancer treatment, and for detecting and characterizing cancer, Diffusion-weighted imaging (DWI) is commonly used. The key in DWI's use extracranially has been due to the emergence of of high-gradient amplitude and multichannel coils, parallelimaging, and echo-planar imaging. The benefit has been fewer motion artefacts and high-quality prostate images.Recently, new techniques have been developed to improve the signal-to-noise ratio of DWI with fewer artefacts, allowing an increase in spatial resolution. For apparent diffusion coefficient quantification, non-Gaussian diffusion models have been proposed as additional tools for prostate cancer detection and evaluation of its aggressiveness. More recently, radiomics and machine learning for prostate magnetic resonance imaging have emerged as novel techniques for the non-invasive characterisation of prostate cancer. This review presents recent developments in prostate DWI and discusses its potential use in clinical practice.

Making the Invisible Visible: Advanced Neuroimaging Techniques in Focal Epilepsy.

It has been a clinically important, long-standing challenge to accurately localize epileptogenic focus in drug-resistant focal epilepsy because more intensive intervention to the detected focus, including resection neurosurgery, can provide significant seizure reduction. In addition to neurophysiological examinations, neuroimaging plays a crucial role in the detection of focus by providing morphological and neuroanatomical information. On the other hand, epileptogenic lesions in the brain may sometimes show only subtle or even invisible abnormalities on conventional MRI sequences, and thus, efforts have been made for better visualization and improved detection of the focus lesions. Recent advance in neuroimaging has been attracting attention because of the potentials to better visualize the epileptogenic lesions as well as provide novel information about the pathophysiology of epilepsy. While the progress of newer neuroimaging techniques, including the non-Gaussian diffusion model and arterial spin labeling, could non-invasively detect decreased neurite parameters or hypoperfusion within the focus lesions, advances in analytic technology may also provide usefulness for both focus detection and understanding of epilepsy. There has been an increasing number of clinical and experimental applications of machine learning and network analysis in the field of epilepsy. This review article will shed light on recent advances in neuroimaging for focal epilepsy, including both technical progress of images and newer analytical methodologies and discuss about the potential usefulness in clinical practice.

Parsimonious modeling of skeletal muscle perfusion: Connecting the stretched exponential and fractional Fickian diffusion.

To develop an anomalous (non-Gaussian) diffusion model for characterizing skeletal muscle perfusion using multi-b-value DWI. Fick's first law was extended for describing tissue perfusion as anomalous superdiffusion, which is non-Gaussian diffusion exhibiting greater particle spread than that of the Gaussian case. This was accomplished using a space-fractional derivative that gives rise to a power-law relationship between mean squared displacement and time, and produces a stretched exponential signal decay as a function of b-value. Numerical simulations were used to estimate parameter errors under in vivo conditions, and examine the effect of limited SNR and residual fat signal. Stretched exponential DWI parameters, α and , were measured in thigh muscles of 4 healthy volunteers at rest and following in-magnet exercise. These parameters were related to a stable distribution of jump-length probabilities and used to estimate microvascular volume fractions. Numerical simulations showed low dispersion in parameter estimates within 1.5% and 1%, and bias errors within 3% and 10%, for α and , respectively. Superdiffusion was observed in resting muscle, and to a greater degree following exercise. Resting microvascular volume fraction was between 0.0067 and 0.0139 and increased between 2.2-fold and 4.7-fold following exercise. This model captures superdiffusive molecular motions consistent with perfusion, using a parsimonious representation of the DWI signal, providing approximations of microvascular volume fraction comparable with histological estimates. This signal model demonstrates low parameter-estimation errors, and therefore holds potential for a wide range of applications in skeletal muscle and elsewhere in the body.

Differentiation of salivary gland tumor using diffusion-weighted imaging with a fractional order calculus model.

To evaluate the feasibility of using imaging parameters (D, β and μ) obtained from fractional order calculus (FROC) diffusion model to differentiate salivary gland tumors. 15 b-value (0-2000 s/mm2) diffusion-weighted imaging (DWI) was scanned in 62 patients with salivary gland tumors (47 benign and 15 malignant). Diffusion coefficient D, fractional order parameter β (which correlates with tissue heterogeneity) and a microstructural quantity μ of the solid portion within the tumor were calculated, and compared between benign and malignant groups, or among pleomorphic adenoma (PA), Warthin's tumor (WT), and malignant tumor (MT) groups. Performance of FROC parameters for differentiation was assessed using receiver operating characteristic analysis. None of the FROC parameters exhibited significant differences between benign and malignant group (D, p = 0.150; β, p = 0.967; μ, p = 0.693). WT showed significantly lower D (p < 0.001) and β (p < 0.001), while higher μ (p = 0.001) than PA. Combination of D, β and μ showed optimal diagnostic performance (area under the curve, AUC, 0.998). MT showed significantly lower D (p = 0.001) and β (p = 0.025) than PA, while no significant difference was found on μ (p = 0.064). Combination of D and β showed optimal diagnostic performance (AUC, 0.933). Significant difference was found on β (p = 0.027) between MT and WT, while not on D (p = 0.806) and μ (p = 0.789). Setting a βof 0.615 as the cut-off value, optimal diagnostic performance could be obtained (AUC = 0.806). A non-Gaussian FROC diffusion model can serve as a noninvasive and quantitative imaging technique for differentiating salivary gland tumors. (1) PA showed higher D and β and lower μ than WT. (2) PA had higher D and β than MT. (3) WT demonstrated lower β than MT. (4) β, as a new FROC parameter, could offer an added value to the differentiation.

Non-Gaussian Diffusion Models and T1 rho Quantification in the Assessment of Hepatic Sinusoidal Obstruction Syndrome in Rats.

Non-Gaussian diffusion models and T1 rho quantification may reflect the changes in tissue heterogeneity in hepatic sinusoidal obstruction syndrome (SOS). To investigate the feasibility of diffusion kurtosis imaging (DKI), stretched exponential model (SEM), and T1 rho quantification in detecting and staging SOS in a monocrotaline (MCT)-induced rat model. Animal study. Thirty male Sprague-Dawley rats gavaged with MCT to induce hepatic SOS and six male rats without any intervention. 3.0T, DWI with five b-values (0-2000 s/mm2 ) and T1 rho with five spin lock times (1-60 msec). MRI was performed 1 day before and 1, 3, 5, 7, and 10 days after MCT administration. The corrected apparent diffusion coefficient (Dapp ), kurtosis coefficient (Kapp ), distributed diffusion coefficient (DDC), and intravoxel water molecular diffusion heterogeneity (α) were calculated from the corresponding non-Gaussian diffusion model. The T1 rho value was calculated using a monoexponential model. Specimens obtained from the six timepoints were categorized into normal liver (n = 6), early-stage (n = 16), and late-stage (n = 14) SOS in accordance with the pathological score. Parametric statistical methods and receiver operating characteristic (ROC) curves were employed to determine diagnostic accuracy. The Dapp , Kapp , DDC, α, and T1 rho values were correlated with pathological score with r values of -0.821, 0.726, -0.828, -0.739, and 0.714 (all P < 0.001), respectively. DKI (combined Dapp and Kapp ) and SEM (combined DDC and α) were better than T1 rho for staging SOS. The areas under the ROC curve of DKI, SEM, and T1 rho for differentiating normal liver and early-stage SOS were 0.97, 1.00, and 0.79, whereas those of DKI, SEM, and T1 rho for differentiating early-stage and late-stage SOS were 1.00, 0.97, and 0.92, respectively. DKI, SEM, and T1 rho may be helpful in staging SOS. 2 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:1110-1121.

Evaluation of non-Gaussian model-based diffusion-weighted imaging in oral squamous cell carcinoma: comparison with tumour functional information derived from positron-emission tomography

To evaluate and compare diffusion-weighted imaging (DWI) parameters derived from a non-Gaussian fitting model and positron-emission tomography (PET) parameters derived from 18F-fluoromisonidazole-PET (FMISO-PET) in patients with oral squamous cell carcinoma (OSCC). Primary sites were evaluated prospectively in 18 patients. DWI was performed using six b-values (0-2,500). Diffusion-related parameters of kurtosis value (K), the kurtosis-corrected diffusion coefficient (DK), diffusion heterogeneity (α), distributed diffusion coefficient (DDC), the slow diffusion coefficient (Dslow), and the apparent diffusion coefficient (ADC) were calculated from four diffusion-fitting models. Maximal standardised uptake values (SUVmax), mean standardised uptake values (SUVmean), and the tumour-to-muscle ration (TMR) of the SUV value were calculated for FMISO-PET. Spearman's correlation coefficient was used to evaluate the correlation between each non-Gaussian diffusion model parameters and PET parameter. There was moderate correlation between FMISO-PET SUVmax and Dslow (ρ=-0.45, p=0.06). In addition, there was good correlation between TMRmax and five non-Gaussian diffusion model parameters (K: ρ=0.65, p=0.004, DK: ρ=-0.72, p=0.0008, DDC: ρ=-0.75, p=0.0003, ADC: ρ=-0.74, p=0.0005, and Dslow: ρ= -0.65, p=0.003), and between TMRmean and five non-Gaussian model parameters (K: ρ=0.64, p=0.005, DK: ρ=-0.61, p=0.007, DDC: ρ=-0.63, p=0.005, ADC: ρ=-0.61, p=0.007, and Dslow: ρ=-0.56, p=0.015). Non-Gaussian diffusion model parameters can be related to tumour hypoxia.

The volumetric-tumour histogram-based analysis of intravoxel incoherent motion and non-Gaussian diffusion MRI: association with prognostic factors in HER2-positive breast cancer

BackgroundTo evaluate the imaging biomarkers of human epidermal growth factor receptor 2 (HER2) positive breast cancer in comparison to other molecular subtypes and to determine the feasibility of identifying hormone receptor (HR) status and lymph node metastasis status using volumetric-tumour histogram-based analysis through intravoxel incoherent motion (IVIM) and non-Gaussian diffusion.MethodsThis study included 145 breast cancer patients with 148 lesions between January and November in 2018. Among the 148 lesions, 74 were confirmed to be HER2-positive. The volumetric-tumour histogram-based features were extracted from the combined IVIM and non-Gaussian diffusion model. IVIM and non-Gaussian diffusion parameters obtained from images of the subjects with different molecular prognostic biomarker statuses were compared by Student’s t test or the Mann–Whitney U test. The area under the curve (AUC), sensitivity, and specificity at the best cut-off point were reported. The Spearman correlation coefficient was calculated to analyse the correlations of clinical tumor nodule metastasis (TNM) stage and Ki67 with the IVIM and non-Gaussian diffusion parameters.ResultsThe entropy of mean kurtosis (MK) was significantly higher in the HER2-positive group than in the HER2-negative group (p = 0.015), with an AUC of 0.629 (95% CI 0.546, 0.707), a sensitivity of 62.6%, and a specificity of 66.2%. For HR status, the MD 5th percentile was higher in the HR-positive group of HER2-positive breast cancer (p = 0.041), with an AUC of 0.643 (95% CI 0.523, 0.751), while for lymph node status, the entropy of mean diffusivity (MK) was lower in the lymph node positive group (p = 0.040), with an AUC of 0.587 (95% CI 0.504, 0.668). The clinical TNM stage and Ki67 index were correlated with several histogram parameters.ConclusionVolumetric-lesion histogram analysis of IVIM and the non-Gaussian diffusion model can be used to provide prognostic information about HER2-positive breast cancers and potentially contribute to individualized anti-HER2 targeted therapy plans .

Unveiling early cortical and subcortical neuronal degeneration in ALS mice by ultra-high field diffusion MRI

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily characterized by the progressive impairment of motor functions. However, a significant portion of affected patients develops severe cognitive dysfunction, developing a widespread white (WM) and gray matter (GM) microstructural impairment. The objective of this study is to determine if Gaussian and non-Gaussian diffusion models gathered by ultra-high field diffusion MRI (UHFD-MRI) are an appropriate tool to detect early structural changes in brain white and gray matter in a preclinical model of ALS. ALS brains (G93A-SOD1mice) were scanned in a 16.7 T magnet. Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) have shown presymptomatic decrease in axonal organization by Fractional Anisotropy (FA) and neurite content by Intracellular Volume Fraction (ICVF) across deep WM (corpus callosum) as well as superficial (cortex) and deep (hippocampus) GM. Additional diffusion kurtosis imaging (DKI) analysis demonstrated broader and earlier GM reductions in mean kurtosis (MK), possibly related to the decrease in neuronal complexity. Histological validation was obtained by an ALS fluorescent mice reporter (YFP, G93A-SOD1 mice). The combination of DTI, NODDI, and DKI models have proved to provide a more complete assessment of the early microstructural changes in the ALS brain, particularly in areas associated with high cognitive functions. This comprehensive approach should be considered as a valuable tool for the early detection of neuroimaging markers.

Diffusion kurtosis imaging in patients with locally advanced rectal cancer: current status and future perspectives.

Morphological magnetic resonance imaging is currently the best imaging technique for local staging in patients with rectal cancer. However, morphological sequences have some limitations, especially after preoperative chemoradiotherapy (pCRT). Diffusion-weighted imaging has been applied to rectal cancer for detection of lesions, characterization of tissue, and evaluation of the response to therapy. In 2005, a non-Gaussian diffusion model called diffusion kurtosis imaging (DKI) was suggested. Several electronic databases were evaluated in the present review. The search included articles published from January 2000 to May 2018. The references of all articles were also evaluated. All titles and abstracts were assessed, and only the studies of DKI in patients with rectal cancer were retained. We identified 35 potentially relevant references through the electronic search. According to the inclusion and exclusion criteria, we retained five clinical studies that met the inclusion criteria. DKI is a useful tool for assessment of tumor aggressiveness, the nodal status, and the risk of early metastases as well as prediction of the response to pCRT. The results of DKI should be considered in treatment decision-making during the work-up of patients with rectal cancer.

High-Spatial-Resolution Diffusion MRI in Parkinson Disease: Lateral Asymmetry of the Substantia Nigra

Background Motor symptoms in Parkinson disease (PD) have exhibited lateral asymmetry, suggesting asymmetric neuronal loss in the substantia nigra (SN). Diffusion MRI may be able to help confirm tissue microstructural alterations in the substantia nigra to probe for the presence of asymmetry. Purpose To investigate lateral asymmetry in the SN of patients with PD by using diffusion MRI with both Gaussian and non-Gaussian models. Materials and Methods In this cross-sectional study conducted from March 2015 to March 2017, 27 participants with PD and 27 age-matched healthy control (HC) participants, all right handed, underwent MRI at 3.0 T. High-spatial-resolution diffusion images were acquired with a reduced field of view by using seven b values up to 3000 sec/mm2. A continuous-time random-walk (CTRW) non-Gaussian diffusion model was used to produce anomalous diffusion coefficient (Dm) and temporal (α) and spatial (β) diffusion heterogeneity indexes followed by a Gaussian diffusion model to yield an apparent diffusion coefficient (ADC). Individual or linear combinations of diffusion parameters in the SN were unilaterally and bilaterally compared between the PD and HC groups. Results In the bilateral comparison between the PD and HC groups, differences were observed in β (0.67 ± 0.06 [standard deviation] vs 0.64 ± 0.04, respectively; P = .016), ADC (0.48 μm2/msec ± 0.08 vs 0.53 μm2/msec ± 0.06, respectively; P = .03), and the combination of CTRW parameters (P = .02). In the unilateral comparison, differences were observed in all diffusion parameters on the left SN (P < .03), but not on the right (P > .20). In a receiver operating characteristic (ROC) analysis to delineate left SN abnormality in PD, the combination of Dm, α, and β produced the best sensitivity (sensitivity, 0.78); the combination of Dm and β produced the best specificity (specificity, 0.85); and the combination of α and β produced the largest area under the ROC curve (area under the ROC curve, 0.73). Conclusion These results suggest that quantitative diffusion MRI is sensitive to brain tissue changes in participants with Parkinson disease and provide evidence of substantia nigra lateral asymmetry in this disease. © RSNA, 2019 Online supplemental material is available for this article.

Magnetic Resonance Diffusion Kurtosis Imaging for Evaluating Stage of Liver Fibrosis in a Rabbit Model

As an extension of the conventional diffusion weighted imaging, diffusion kurtosis imaging (DKI) is based on the non-Gaussian diffusion model that can inherently account for restricted water diffusion within the complex microstructure of most tissues. This study aimed to investigate association of liver DKI derived parameter with stage of liver fibrosis. Fifty-six healthy New Zealand white rabbits were enrolled into this study, among which 48 rabbits were randomly given carbon tetrachloride to model liver fibrosis, and 8 rabbits treated with normal saline served as control subjects. All rabbits underwent liver DKI followed by biopsy to stage fibrosis (stages F0-F4) on 6th, 8th, 10th, and 12th weekends after initiation of modeling fibrosis. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusion (MD) were derived from DKI data. Statistical analysis was to evaluate association of DKI derived parameter with stage of fibrosis. FA (r = 0.512) and MK (r = 0.567) increased, and MD (r = -0.574) decreased with increasing stage of fibrosis from F0 to F4 (all p values < 0.05). Significant differences were found in all parameters between F0 and F3 or F4, F1 and F4, F0 and F1-4, and F0-1 and F2-4 (all p values < 0.05). FA and MD could distinguish between F0 from F2, MD, and MK could distinguish F1 from F3, F0-2 from F3-4, and F1-2 from F3-4, and MK and FA could distinguish F2 from F4, and F0-3 from F4 (all p values < 0.05). According to receiver operating characteristic analysis, MK could best predict stage ≥F1, ≥F2, ≥F3, and F4, and discriminate F1-2 from F3-4 with areas under receiver operating characteristic curve of 0.766-0.930. DKI derived parameters can help stage fibrosis.

A study on diffusion and kurtosis features of cervical cancer based on non-Gaussian diffusion weighted model

ObjectiveTo explore the diffusion and kurtosis features of cervical cancer (CC) and study the feasibility of diffusion kurtosis imaging (DKI) based on the non-Gaussian diffusion-weighted model to differentiate the stage and grade of CC. MethodsA total of 50 patients with pathologically confirmed CC were enrolled. MRI examinations including DKI (with 5b values 200, 500, 1000, 1500, and 2000smm−2 were performed before any treatment. The apparent coefficient (Dapp) and the apparent kurtosis value (Kapp) were derived from the non-gaussian diffusion model, and the apparent diffusion coefficient (ADC) was derived from the Gaussian model. The parameters of CC and normal tissue (myometrium) were obtained, analyzed statistically, and evaluated with respect to differentiating stage and grade between the tissue and the CC. ResultsADC and Dapp values of CC were significantly lower than that of the normal myometrium (P=0.024 and P<0.001, respectively), while the Kapp value was not found to exhibit a significant difference. Compared to the well/moderately differentiated CC, poorly differentiated CC had a significantly decreased mean ADC and Dapp (P=0.018 and P=0.026, respectively); however, the mean Kapp (P=0.035) increased significantly. In the clinical staging, the DKI sequence was advantageous over conventional MRI sequences (degree of accuracy: 90% vs. 74%), Although in the quantitative analysis, these parameters did not show a significant difference. ConclusionsThe pilot study demonstrated that these diffusion and kurtosis indices from DKI based on the non-Gaussian diffusion-weighted model putatively differentiated the grade and stage of CC.

Non-Gaussian diffusion imaging with a fractional order calculus model to predict response of gastrointestinal stromal tumor to second-line sunitinib therapy.

To demonstrate the clinical value of a non-Gaussian diffusion model using fractional order calculus (FROC) for early prediction of the response of gastrointestinal stromal tumor to second-line sunitinib targeted therapy. Fifteen patients underwent sunitinib treatment after imatinib resistance. Diffusion-weighted imaging with multiple b-values was performed before treatment (baseline) and 2 weeks (for early prediction of response) after initiating sunitinib treatment. Conventional MRI images at 12 weeks were used to determine the good and poor responders according to the modified Choi criteria for MRI. Diffusion coefficient D, fractional order parameter β (which correlates to intravoxel tissue heterogeneity), and a microstructural quantity µ were calculated using the FROC model. The FROC parameters and the longest diameter of the lesion, as well as their changes after 2 weeks of treatment, were compared between the good and poor responders. Additionally, the pretreatment FROC parameters were individually combined with the change in D (ΔD) using a logistic regression model to evaluate response to sunitinib treatment with a receiver operating characteristic analysis. Forty-two good-responding and 32 poor-responding lesions were identified. Significant differences were detected in pretreatment β (0.67 versus 0.74, P = 0.011) and ΔD (45.7% versus 12.4%, P = 0.001) between the two groups. The receiver operating characteristic analysis showed that ΔD had a significantly higher predictive power than the tumor size change (area under the curve: 0.725 versus 0.580; 0.95 confidence interval). When ΔD was combined with pretreatment β, the area under the curve improved to 0.843 with a predictive accuracy of 75.7% (56 of 74). The non-Gaussian FROC diffusion model showed clinical value in early prediction of gastrointestinal stromal tumor response to second-line sunitinib targeted therapy. The pretreatment FROC parameter β can increase the predictive accuracy when combined with the change in diffusion coefficient during treatment. Magn Reson Med 79:1399-1406, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

A comparative assessment of preclinical chemotherapeutic response of tumors using quantitative non-Gaussian diffusion MRI

BackgroundDiffusion-weighted MRI (DWI) signal attenuation is often not mono-exponential (i.e. non-Gaussian diffusion) with stronger diffusion weighting. Several non-Gaussian diffusion models have been developed and may provide new information or higher sensitivity compared with the conventional apparent diffusion coefficient (ADC) method. However the relative merits of these models to detect tumor therapeutic response is not fully clear. MethodsConventional ADC, and three widely-used non-Gaussian models, (bi-exponential, stretched exponential, and statistical model), were implemented and compared for assessing SW620 human colon cancer xenografts responding to barasertib, an agent known to induce apoptosis via polyploidy. Bayesian Information Criterion (BIC) was used for model selection among all three non-Gaussian models. ResultsAll of tumor volume, histology, conventional ADC, and three non-Gaussian DWI models could show significant differences between control and treatment groups after four days of treatment. However, only the non-Gaussian models detected significant changes after two days of treatment. For any treatment or control group, over 65.7% of tumor voxels indicate the bi-exponential model is strongly or very strongly preferred. ConclusionNon-Gaussian DWI model-derived biomarkers are capable of detecting tumor earlier chemotherapeutic response of tumors compared with conventional ADC and tumor volume. The bi-exponential model provides better fitting compared with statistical and stretched exponential models for the tumor and treatment models used in the current work.