Diffusion-weighted Magnetic Resonance Imaging Measurements Research Articles

Helicobacter pylori, persistent infection burden and structural brain imaging markers.

Persistent infections, whether viral, bacterial or parasitic, including Helicobacter pylori infection, have been implicated in non-communicable diseases, including dementia and other neurodegenerative diseases. In this cross-sectional study, data on 635 cognitively normal participants from the UK Biobank study (2006-21, age range: 40-70 years) were used to examine whether H. pylori seropositivity (e.g. presence of antibodies), serointensities of five H. pylori antigens and a measure of total persistent infection burden were associated with selected brain volumetric structural MRI (total, white, grey matter, frontal grey matter (left/right), white matter hyperintensity as percent intracranial volume and bi-lateral sub-cortical volumes) and diffusion-weighted MRI measures (global and tract-specific bi-lateral fractional anisotropy and mean diffusivity), after an average 9-10 years of lag time. Persistent infection burden was calculated as a cumulative score of seropositivity for over 20 different pathogens. Multivariable-adjusted linear regression analyses were conducted, whereby selected potential confounders (all measures) and intracranial volume (sub-cortical volumes) were adjusted, with stratification by Alzheimer's disease polygenic risk score tertile when exposures were H. pylori antigen serointensities. Type I error was adjusted to 0.007. We report little evidence of an association between H. pylori seropositivity and persistent infection burden with various volumetric outcomes (P > 0.007, from multivariable regression models), unlike previously reported in past research. However, H. pylori antigen serointensities, particularly immunoglobulin G against the vacuolating cytotoxin A, GroEL and outer membrane protein antigens, were associated with poorer tract-specific white matter integrity (P < 0.007), with outer membrane protein serointensity linked to worse outcomes in cognition-related tracts such as the external capsule, the anterior limb of the internal capsule and the cingulum, specifically at low Alzheimer's disease polygenic risk. Vacuolating cytotoxin A serointensity was associated with greater white matter hyperintensity volume among individuals with mid-level Alzheimer's disease polygenic risk, while among individuals with the highest Alzheimer's disease polygenic risk, the urease serointensity was consistently associated with reduced bi-lateral caudate volumes and the vacuolating cytotoxin A serointensity was linked to reduced right putamen volume (P < 0.007). Outer membrane protein and urease were associated with larger sub-cortical volumes (e.g. left putamen and right nucleus accumbens) at middle Alzheimer's disease polygenic risk levels (P < 0.007). Our results shed light on the relationship between H. pylori seropositivity, H. pylori antigen levels and persistent infection burden with brain volumetric structural measures. These data are important given the links between infectious agents and neurodegenerative diseases, including Alzheimer's disease, and can be used for the development of drugs and preventive interventions that would reduce the burden of those diseases.

A machine learning-based method for estimating the number and orientations of major fascicles in diffusion-weighted magnetic resonance imaging.

Accurate modeling of diffusion-weighted magnetic resonance imaging measurements is necessary for accurate brain connectivity analysis. Existing methods for estimating the number and orientations of fascicles in an imaging voxel either depend on non-convex optimization techniques that are sensitive to initialization and measurement noise, or are prone to predicting spurious fascicles. In this paper, we propose a machine learning-based technique that can accurately estimate the number and orientations of fascicles in a voxel. Our method can be trained with either simulated or real diffusion-weighted imaging data. Our method estimates the angle to the closest fascicle for each direction in a set of discrete directions uniformly spread on the unit sphere. This information is then processed to extract the number and orientations of fascicles in a voxel. On realistic simulated phantom data with known ground truth, our method predicts the number and orientations of crossing fascicles more accurately than several classical and machine learning methods. It also leads to more accurate tractography. On real data, our method is better than or compares favorably with other methods in terms of robustness to measurement down-sampling and also in terms of expert quality assessment of tractography results.

A Longitudinal Study of White Matter Development in Relation to Changes in Autism Severity Across Early Childhood

BackgroundCross-sectional diffusion-weighted magnetic resonance imaging studies suggest that young autistic children have alterations in white matter structure that differ from older autistic individuals. However, it is unclear whether these differences result from atypical neurodevelopment or sampling differences between young and older cohorts. Furthermore, the relationship between altered white matter development and longitudinal changes in autism symptoms is unknown. MethodsUsing longitudinal diffusion-weighted magnetic resonance imaging acquired over 2 to 3 time points between the ages of approximately 2.5 to 7.0 years in 125 autistic children and 69 typically developing control participants, we directly tested the hypothesis that autistic individuals have atypical white matter development across childhood. Additionally, we sought to determine whether changes in white matter diffusion parameters were associated with longitudinal changes in autism severity. ResultsAutistic children were found to have slower development of fractional anisotropy in the cingulum bundle, superior longitudinal fasciculus, internal capsule, and splenium of the corpus callosum. Furthermore, in the sagittal stratum, autistic individuals who increased in autism severity over time had a slower developmental trajectory of fractional anisotropy compared with individuals whose autism decreased in severity. In the uncinate fasciculus, autistic individuals who decreased in autism symptom severity also had greater increases in fractional anisotropy with age. ConclusionsThese longitudinal findings indicate that previously reported differences in diffusion-weighted magnetic resonance imaging measures between younger and older autism cohorts are attributable to an atypical developmental trajectory of white matter. Differences in white matter development between individuals whose autism severity increased, remained stable, or decreased suggest that these functional differences are associated with fiber development in the autistic brain.

Investigating the sensitivity of free-water corrected diffusion-weighted MRI measures to understand sex-specific alterations in Parkinson's disease with mild cognitive impairment

Objective: To investigate the sensitivity of conventional and free-water (FW) corrected diffusion-MRI (dMRI)-derived measures in revealing sex-specific alterations of white-matter (WM) disorganization in Parkinson's disease (PD) patients, with and without mild cognitive impairment (MCI), and healthy controls (HC).

A diffusion-weighted imaging tract-based spatial statistics study of autism spectrum disorder in preschool-aged children

BackgroundThe core symptoms of autism spectrum disorder (ASD) are widely theorized to result from altered brain connectivity. Diffusion-weighted magnetic resonance imaging (DWI) has been a versatile method for investigating underlying microstructural properties of white matter (WM) in ASD. Despite phenotypic and etiological heterogeneity, DWI studies in majority male samples of older children, adolescents, and adults with ASD have largely reported findings of decreased fractional anisotropy (FA) across several commissural, projection, and association fiber tracts. However, studies in preschool-aged children (i.e., < 30–40 months) suggest individuals with ASD have increased measures of WM FA earlier in development.MethodsWe analyzed 127 individuals with ASD (85♂, 42♀) and 54 typically developing (TD) controls (42♂, 26♀), aged 25.1–49.6 months. Voxel-wise effects of ASD diagnosis, sex, age, and their interaction on DWI measures of FA, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were investigated using tract-based spatial statistics (TBSS) while controlling mean absolute and relative motion.ResultsCompared to TD controls, males and females with ASD had significantly increased measures of FA in eight clusters (threshold-free cluster enhancement p < 0.05) that incorporated several WM tracts including regions of the genu, body, and splenium of the corpus callosum, inferior frontal-occipital fasciculi, inferior and superior longitudinal fasciculi, middle and superior cerebellar peduncles, and corticospinal tract. A diagnosis by sex interaction was observed in measures of AD across six significant clusters incorporating areas of the body, genu, and splenium of the corpus collosum. In these tracts, females with ASD showed increased AD compared to TD females, while males with ASD showed decreased AD compared to TD males.ConclusionsThe current findings support growing evidence that preschool-aged children with ASD have atypical measures of WM microstructure that appear to differ in directionality from alterations observed in older individuals with the condition. To our knowledge, this study represents the largest sample of preschool-aged females with ASD to be evaluated using DWI. Microstructural differences associated with ASD largely overlapped between sexes. However, differential relationships of AD measures indicate that sex likely modulates ASD neuroanatomical phenotypes. Further longitudinal study is needed to confirm and quantify the developmental relationship of WM structure in ASD.

Diffusion-weighted MRI measures suggest increased white-matter integrity in Internet gaming disorder: Evidence from the comparison with recreational Internet game users

Several studies have suggested that Internet gaming disorder (IGD) is related to altered brain white matter integrity. However, seeming inconsistencies exist and may reflect comparison groups not matched well for certain gaming characteristics. In order to address this possible concern, we recruited in the present study individuals with recreational Internet game use (RGU) comprised of individuals who spend similar amounts of time as IGD subjects playing online games without developing IGD. Diffusion tensor imaging data were collected from 42 IGD and 44 RGU subjects. Whole-brain comparisons showed that IGD subjects demonstrated increased fractional anisotropy (FA) in the bilateral anterior thalamic radiation, anterior limb of the internal capsule, bilateral corticospinal tract, bilateral inferior fronto-occipital fasciculus, corpus callosum, and bilateral inferior longitudinal fasciculus. In addition, Internet-addiction severity was positively correlated with FA values. Taken together, we conclude that IGD is associated with measures of increased white-matter integrity in tracts linking reward circuitry and sensory and motor control systems.

Telomere length and advanced diffusion MRI as biomarkers for repetitive mild traumatic brain injury in adolescent rats.

Mild traumatic brain injuries (mTBI) are of worldwide concern in adolescents of both sexes, and repeated mTBI (RmTBI) may have serious long-term neurological consequences. As such, the study of RmTBI and discovery of objective biomarkers that can help guide medical decisions is an important undertaking. Diffusion-weighted MRI (DWI), which provides markers of axonal injury, and telomere length (TL) are two clinically relevant biomarkers that have been implicated in a number of neurological conditions, and may also be affected by RmTBI. Therefore, this study utilized the lateral impact injury model of RmTBI to investigate changes in diffusion MRI and TL, and how these changes relate to each other. Adolescent male and female rats received either three mTBIs or three sham injuries. The first injury was given on postnatal day 30 (P30), with the repeated injuries separated by four days each. Seven days after the final injury, a sample of ear tissue was collected for TL analysis. Rats were then euthanized and whole brains were collected and fixated for MRI analyses that included diffusion and high-resolution structural sequences. Compared to the sham-injured group, RmTBI rats had significantly shorter TL at seven days post-injury. Analysis of advanced DWI measures found that RmTBI rats had abnormalities in the corpus callosum and cortex at seven days post-injury. Notably, many of the DWI changes were correlated with TL. These findings demonstrate that TL and DWI measurements are changed by RmTBI and may represent clinically applicable biomarkers for this.

Diverging white matter trajectories in children after traumatic brain injury: The RAPBI study.

To examine longitudinal trajectories of white matter organization in pediatric moderate/severe traumatic brain injury (msTBI) over a 12-month period. We studied 21 children (16 M/5 F) with msTBI, assessed 2-5 months postinjury and again 13-19 months postinjury, as well as 20 well-matched healthy control children. We assessed corpus callosum function through interhemispheric transfer time (IHTT), measured using event-related potentials, and related this to diffusion-weighted MRI measures of white matter (WM) microstructure. At the first time point, half of the patients with TBI had significantly slower IHTT (TBI-slow-IHTT, n = 11) and half were in the normal range (TBI-normal-IHTT, n = 10). The TBI-normal-IHTT group did not differ significantly from healthy controls, either in WM organization in the chronic phase or in the longitudinal trajectory of WM organization between the 2 evaluations. In contrast, the WM organization of the TBI-slow-IHTT group was significantly lower than in healthy controls across a large portion of the WM. Longitudinal analyses showed that the TBI-slow-IHTT group experienced a progressive decline between the 2 evaluations in WM organization throughout the brain. We present preliminary evidence suggesting a potential biomarker that identifies a subset of patients with impaired callosal organization in the first months postinjury who subsequently experience widespread continuing and progressive degeneration in the first year postinjury.

Modeling Functional Connectivity on Empirical and Randomized Structural Brain Networks

This study combines modeling of neuronal activity and networks derived from neuroimaging data in order to investigate how the structural organization of the human brain affects the temporal dynamics of interacting brain areas. The dynamics of the neuronal activity is modeled with FitzHugh–Nagumo oscillators and the blood-oxygen-level-dependent (BOLD) time series is inferred via the Balloon–Windkessel hemodynamic model. The simulations are based on anatomical probability maps between considered brain regions of interest. These maps were derived from diffusion-weighted magnetic resonance imaging measurements. In addition, the length of the fiber tracks allows for inference of coupling delays due to finite signal propagation velocities. We aim to investigate (i) graph-theoretical properties of the network topology derived from neuroimaging data and (ii) how randomization of structural connections influences the dynamics of neuronal activity. The network characteristics of the structural connectivity data are compared to density-matched Erdős–Renyi random graphs. Furthermore, the neuronal and BOLD activity are modeled on both empirical and random (Erdős–Renyi type) graphs. The simulated temporal dynamics on both graphs are compared statistically to capture whether the spatial organization of these network affects the modeled time series. Results support previous findings that key topological network properties such as small-worldness of our neuroimaging data are distinguishable from random networks. We also show that simulated BOLD activity is affected by the underlying network topology and the strength of connections between the network nodes. The difference of the modeled temporal dynamics of brain networks from the dynamics on randomized graphs suggests that anatomical connections in the human brain together with dynamical self-organization are crucial for the temporal evolution of the resting-state activity.

Validation of MRI-Based Fiber-Tracking Results

A new approach to estimating the probability of the fiber-track existence has been developed and validated on the basis of digital phantoms and diffusion-weighted magnetic resonance imaging measurements on human brain. The proposed approach includes two parameters—the local probability of the tract direction and the Shannon entropy. The local probability of the tract direction characterizes how well tracts “fit” the direction information in a voxel. The Shannon entropy characterizes the shape of diffusivity in the voxel. Calculations on digital phantoms and in vivo data showed that the combination of these parameters makes it possible to verify fiber-tracking results.

Apparent diffusion coefficient of normal adrenal glands.

ObjectiveTo assess the feasibility and reliability of apparent diffusion coefficient (ADC) measurements of normal adrenal glands.Materials and methodsThis was a retrospective study involving 32 healthy subjects, divided into two groups: prepubertal (PreP, n = 12), aged from 2 months to 12.5 years (4 males; 8 females); and postpubertal (PostP, n = 20), aged from 11.9 to 61 years (5 males; 15 females). Diffusion-weighted magnetic resonance imaging (DW-MRI) sequences were acquired at a 1.5 T scanner using b values of 0, 20, 500, and 1000 s/mm2. Two radiologists evaluated the images. ADC values were measured pixel-by-pixel on DW-MRI scans, and automatic co-registration with the ADC map was obtained.ResultsMean ADC values for the right adrenal glands were 1.44 × 10-3 mm2/s for the PreP group and 1.23 × 10-3 mm2/s for the PostP group, whereas they were 1.58 × 10-3 mm2/s and 1.32 × 10-3 mm2/s, respectively, for the left glands. ADC values were higher in the PreP group than in the PostP group (p < 0.05). Agreement between readers was almost perfect (intraclass correlation coefficient, 0.84-0.94; p < 0.05).ConclusionOur results demonstrate the feasibility and reliability of performing DW-MRI measurements of normal adrenal glands. They could also support the feasibility of ADC measurements of small structures.

The diffusion-weighted magnetic resonance imaging (DWI) predicts the early response of esophageal squamous cell carcinoma to concurrent chemoradiotherapy

PurposeTo investigate the predictive value of serial diffusion-weighted MRI (DWI) on tumor response of the concurrent chemoradiotherapy (CCRT) for esophageal squamous cell carcinoma (ESCC) and to determine the optimal time point of DWI measurements. Methods and materialsFrom June 2010 to October 2011, 38 ESCC patients were consecutively enrolled into this prospective cohort study. During their treatment, the longitudinal DWIs were acquired at beginning and every week during the course of CCRT. ADC maps were generated from there DWIs. The tumor responses were evaluated according to the RECIST. Results(1) At completion of CCRT, 20 (52.6%) and 18 (47.4%) patients were evaluated as CR and PR, respectively. Over the time points of measures, the series of ADC values (10−3mm2/s) in whole GTV were consistently characterized with higher (all p<0.05) for these CR patients as their means (std) were 2.24 (0.49), 2.23 (0.51), 2.44 (0.57), 2.54 (0.52), 2.70 (0.46), 2.80 (0.55), 2.92 (0.62), compared with these PR patients as 1.83 (0.31), 1.79 (0.21), 1.87 (0.30), 1.97 (0.37), 2.15 (0.44), 2.26 (0.46), 2.32 (0.51), respectively. However, the ADC change rates (ΔADC) of two groups were found to be similar. These results were also supported by the multivariate ANOVA analyses. The same analysis results of DWI based GTV volumes were also found. (2) The comparisons of logistic regression analysis indicated that only the ADC values at Week 3 (15 fractions) were an independent prognostic factor of tumor response (OR=0.303, p=0.003). ROC curve analysis showed that Area Under Curve for ADC values of the end of 2nd and 3rd weeks were biggest (0.822) and the prediction efficacy was comparatively optimized. The corresponding cut-off values were 2.11 and 2.14 (10−3mm2/s), respectively. (3) Additional analyses on those eight patients with tumor local recurrence within 1year demonstrated the level-off after the continuously increased ADC values till Week 4. ConclusionsDWI can be used as a biomarker to predict TE of esophageal cancers in early time during CCRT. The treatment-induced change in ADC of whole GTV during the first 2–3weeks can be highly predictive to TE. The unchanged ADC value in late period may indicate the high tendency of tumor recurrence after 1year.

Abstract P5-01-02: Multimodality molecular imaging with dynamic 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and MRI to evaluate response and resistance to neoadjuvant chemotherapy (NAC)

Abstract Background: Using quantitative FDG PET to measure glucose metabolism and perfusion, and dynamic contrast-enhanced (DCE) MRI to measure perfusion, we previously identified a metabolic signature for breast cancer resistant to NAC. This imaging signature is (1) persistent or increased tumor perfusion despite treatment, (2) an altered pattern of glucose kinetics in response to therapy, and (3) pre-therapy mismatch between tumor metabolism (MRFDG) and glucose delivery (K1) (high ratio of MRFDG/K1). These patterns predict poor response, early relapse and death independent of established prognostic factors, including pathologic response. Identification of factors associated with resistance or response to therapy is the translational goal of "Quantitative Dynamic PET and MRI in Breast Cancer Therapy," part of the Seattle Breast SPORE (1P50CA138293). Methods: Patients (Pts) undergoing NAC for histologically confirmed breast cancer (stage II-III) were approached for this trial (CCIRB# 7587). FDG PET and DCE-MRI were obtained pre-therapy, 2-12 weeks after start of NAC (mid-therapy) and after completion of NAC. Breast biopsies were obtained pre-therapy and post-NAC. FDG PET included a dynamic scan with kinetic analysis. PET measures included SUVmax, MRFDG, K1, Ki, and Patlak. 3T DCE-MRI measurements included semi-quantitative vascular parameters of peak enhancement (PE), signal enhancement ratio (SER), washout fraction, functional tumor volume, and apparent diffusion coefficient (ADC) from diffusion-weighted MRI (DWI). Breast biopsies were assayed by immunohistochemistry and gene expression profiling. NAC was per physician's choice with most pts receiving weekly paclitaxel (with trastuzumab if HER2+) followed by doxorubicin/cyclophosphamide. Results: 32 pts have completed the study. Pathologic complete response (pCR), defined as absence of invasive cancer in the breast, was observed in 9 (28%); near pCR defined as only microscopic residual invasive cancer in 3 (9%) more pts. Mid-therapy decline in SUVmax and K1 was associated with near pCR; (p-value 0.06, 0.04, respectively). Pre-therapy PET measures of MRFDG and K1 were not predictive of pCR. On MRI, pre-therapy PE (p=0.009), SER (p=0.01), washout fraction (p=0.02), ADC (p=0.08, trend) and mid-therapy change in volume (p=0.05) were each predictive of pCR. Gene profiling of pre-therapy biopsies showed correlation between high MRFDG/K1 ratio in basal and luminal B tumors. Conclusions: Assessment of serial changes in tumor metabolism and perfusion by FDG PET and DCE-MRI is feasible in the clinic. Mid-therapy decline in metabolism and glucose delivery was predictive of pCR; consistent with prior retrospective series. Baseline DCE-MRI and DWI measures show promise to predict response, and associations of mid-therapy change in MR functional tumor volume with pCR agree with findings of another multisite clinical trial (ISPY). These imaging parameters may serve as useful biomarkers to inform future neoadjuvant trials. Integration of imaging data with gene expression profiling revealed that the pattern of metabolism in luminal B tumors was closer to that of the basal subtype compared to other ER-positive tumors. Citation Format: Specht JM, Partridge S, Chai X, Novakova A, Peterson L, Shields A, Guenthoer J, Linden HM, Gralow JR, Gadi V, Korde L, Hills D, Hsu L, Hockenbery DM, Kinahan P, Mankoff DA, Porter PL. Multimodality molecular imaging with dynamic 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and MRI to evaluate response and resistance to neoadjuvant chemotherapy (NAC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-01-02.

Preoperative imaging in patients undergoing trachelectomy for cervical cancer: Validation of a combined T2- and diffusion-weighted endovaginal MRI technique at 3.0 T

AimThe aim of this study is to validate high-resolution endovaginal T2- and diffusion-weighted MRI measurements (tumour size, volume and length of uninvolved cervical canal) against histology in patients undergoing trachelectomy. Patients/interventions55 consecutive patients 25–44years with cervical cancer being considered for trachelectomy were prospectively assessed with endovaginal T2-W and diffusion-weighted MRI. Two independent observers blinded to histology recorded maximum tumour dimension, volume and distance from the superior aspect of the tumour to the internal os. Following trachelectomy, pathologist-outlined tumour sections were photographed with a set scale and similar measurements were recorded. ResultsFifteen of 45 patients subsequently treated with fertility-sparing surgery had residual tumour (median histological volume: 0.28cm3, IQR=0.14–1.06cm3). Sensitivity, specificity, positive and negative predictive values for detecting tumour: Observer1: 86.7%, 80.0%, 68.4%, and 92.3%, respectively; Observer2: 86.7%, 90.0%, 81.0%, and 93.1%, respectively. Size and volume correlated between observers (r=0.96, 0.84, respectively, p<0.0001). Size correlated between each observer and histology (observer 1 r=0.91, p<0.0001; observer 2 r=0.93, p<0.0001), volume did not (observer 1: r=0.08, p=0.6; observer 2: r=0.21, p=0.16); however, differences between observer measurements and histology were not significant (size p=0.09, volume p=0.15). Differences between MRI and histology estimates of endocervical canal length were not significant (p=0.1 both observers). ConclusionIn subcentimetre cervical cancers, endovaginal MRI correlates with pathology and is invaluable in assessing patients for fertility-sparing surgery.

Spurious group differences due to head motion in a diffusion MRI study

Diffusion-weighted MRI (DW-MRI) has become a popular imaging modality for probing the microstructural properties of white matter and comparing them between populations in vivo. However, the contrast in DW-MRI arises from the microscopic random motion of water molecules in brain tissues, which makes it particularly sensitive to macroscopic head motion. Although this has been known since the introduction of DW-MRI, most studies that use this modality for group comparisons do not report measures of head motion for each group and rely on registration-based correction methods that cannot eliminate the full effects of head motion on the DW-MRI contrast. In this work we use data from children with autism and typically developing children to investigate the effects of head motion on differences in anisotropy and diffusivity measures between groups. We show that group differences in head motion can induce group differences in DW-MRI measures, and that this is the case even when comparing groups that include control subjects only, where no anisotropy or diffusivity differences are expected. We also show that such effects can be more prominent in some white-matter pathways than others, and that they can be ameliorated by including motion as a nuisance regressor in the analyses. Our results demonstrate the importance of taking head motion into account in any population study where one group might exhibit more head motion than the other.

Therapeutic effect of nerve growth factor on cerebral infarction in dogs using the hemisphere anomalous volume ratio of diffusion-weighted magnetic resonance imaging.

A model of focal cerebral ischemic infarction was established in dogs through middle cerebral artery occlusion of the right side. Thirty minutes after occlusion, models were injected with nerve growth factor adjacent to the infarct locus. The therapeutic effect of nerve growth factor against cerebral infarction was assessed using the hemisphere anomalous volume ratio, a quantitative index of diffusion-weighted MRI. At 6 hours, 24 hours, 7 days and 3 months after modeling, the hemisphere anomalous volume ratio was significantly reduced after treatment with nerve growth factor. Hematoxylin-eosin staining, immunohistochemistry, electron microscopy and neurological function scores showed that infarct defects were slightly reduced and neurological function significantly improved after nerve growth factor treatment. This result was consistent with diffusion-weighted MRI measurements. Experimental findings indicate that nerve growth factor can protect against cerebral infarction, and that the hemisphere anomalous volume ratio of diffusion-weighted MRI can be used to evaluate the therapeutic effect.

P2-08-03: Quantitative MRI for Noninvasive Prediction of Prognostic Markers in Breast Cancer.

Abstract Background: Magnetic resonance imaging (MRI) is a valuable tool for assessing extent of breast cancer and monitoring treatment response. Quantitative measures by diffusion-weighted MRI (DWI) and dynamic contrast-enhanced (DCE) MRI reflect tumor cellularity and vascularity. Tumor grade and some histopathological markers, such as ER, PR, HER-2, Ki67 and P53, are prognostic factors that can also be associated with tumor cellularity and vascularity. DWI and DCE measures may therefore provide a noninvasive means for predicting disease prognosis and stratifying patients to appropriate therapies. The purpose of this study was to investigate the correlation between quantitative MRI features and prognostic pathological factors in patients with invasive breast cancer. Methods: This IRB-approved retrospective study included patients with biopsy-proven invasive cancer who underwent 1.5T breast MRI (including DCE and DWI) from October 2005 to May 2006 prior to treatment. Pathology data was obtained from pre-treatment biopsy and intrinsic subtype classification was approximated by standard immunohistochemistry characteristics. After excluding cases with missing MRI or pathology data, the final study cohort included 41 invasive cancers (36 ductal and 5 lobular carcinomas) in 36 patients. MRI measures included lesion DCE kinetic features: peak initial enhancement (PE), percent rapid enhancement (RE), and percent washout (WO), and DWI normalized apparent diffusion coefficient values (nADC). Associations between imaging features and pathology markers, cancer grades and intrinsic subtypes were evaluated by Mann-Whitney U test and multivariate logistic regression. Results: Results of univariate comparisons are summarized in Table 1. One or more DCE-MRI kinetic parameters were significantly predictive (p&amp;lt;0.05) of each of the histopathological markers with the exception of ER, which was marginally associated with WO (p=0.05). Each of the DCE kinetics parameters significantly discriminated grade III tumors from grades I and II and luminal A from luminal B and basal-like intrinsic subtypes. In multivariate regression, both PE and WO were significant independent predictors of tumor grade (p=0.0094, p=0.0005, respectively). WO and nADC were significant independent predictors of PR status (p=0.0054, p=0.0027), while PE was the only significant independent predictor of both Ki67 (p=0.014) and intrinsic subtype (p=0.015). Conclusion: This preliminary study suggests that quantitative MRI measures are associated with prognostic tumor markers and may provide valuable noninvasive characterization of tumor biology. Larger prospective studies are needed to validate our findings. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-03.

Combined diffusion-weighted and dynamic contrast-enhanced imaging of patients with acute osteoporotic vertebral fractures

Objectives To evaluate the potential and to analyze parameter correlations of combined quantitative diffusion-weighted MRI (DWI) and high-temporal-resolution dynamic contrast-enhanced MRI (DCE-MRI) in vertebral bone marrow (vBM) of patients with osteoporosis and acute vertebral compression fractures, providing additional information for a better understanding of the physiological background of parameter changes. Materials and methods 20 patients with acute osteoporotic fractures were examined with DWI and DCE-MRI at 1.5 T. DCE-MRI was performed with a 2D saturation-recovery turbo-FLASH sequence, acquiring 300 dynamics with a temporal resolution of 1 s. For DWI measurements, a DW HASTE sequence with b-values from 100 to 600 s/mm 2 was applied. In each patient, ROIs were drawn manually in the fractures and in normal appearing vertebrae. For DCE-MRI, the concentration–time curves of these ROIs were analyzed using a two-compartment tracer-kinetic model in the lesions, providing separate estimates of perfusion and permeability, and a one-compartment model in normal vBM, providing only a mixed representation of perfusion and permeability in terms of a mixed flow parameter K trans and the extracellular volume (ECV). In the case of DWI, attenuation curves were fitted to a monoexponential decay model to determine the apparent diffusion coefficient (ADC). Results Mean perfusion parameters and ADCs were significantly ( p < 0.001) different in the fractures compared to adjacent normal appearing vertebrae ( K trans: 7.81 mL/100 mL/min vs. 14.61 mL/100 mL/min, ECV: 52.84 mL/100 mL vs. 4.61 mL/100 mL, ADC: 1.71 × 10 –3 mm 2/s vs. 0.57 × 10 –3 mm 2/s). ADCs showed a significant correlation with the ECV. Conclusion The quantitative analysis of DWI and DCE-MRI could distinguish osteoporotic fractures from normal appearing vertebrae. A significant correlation found between ECV and ADCs might be able to explain the cause for the increased diffusivity in osteoporotic fractures. Since the other perfusion parameters do not correlate with the ADC, they provide additional pathophysiological information not accessible with DWI.

Diffusion-Weighted Magnetic Resonance Imaging as a Cancer Biomarker: Consensus and Recommendations

On May 3, 2008, a National Cancer Institute (NCI)-sponsored open consensus conference was held in Toronto, Ontario, Canada, during the 2008 International Society for Magnetic Resonance in Medicine Meeting. Approximately 100 experts and stakeholders summarized the current understanding of diffusion-weighted magnetic resonance imaging (DW-MRI) and reached consensus on the use of DW-MRI as a cancer imaging biomarker. DW-MRI should be tested as an imaging biomarker in the context of well-defined clinical trials, by adding DW-MRI to existing NCI-sponsored trials, particularly those with tissue sampling or survival indicators. Where possible, DW-MRI measurements should be compared with histologic indices including cellularity and tissue response. There is a need for tissue equivalent diffusivity phantoms; meanwhile, simple fluid-filled phantoms should be used. Monoexponential assessments of apparent diffusion coefficient values should use two b values (> 100 and between 500 and 1000 mm2/sec depending on the application). Free breathing with multiple acquisitions is superior to complex gating techniques. Baseline patient reproducibility studies should be part of study designs. Both region of interest and histogram analysis of apparent diffusion coefficient measurements should be obtained. Standards for measurement, analysis, and display are needed. Annotated data from validation studies (along with outcome measures) should be made publicly available. Magnetic resonance imaging vendors should be engaged in this process. The NCI should establish a task force of experts (physicists, radiologists, and oncologists) to plan, organize technical aspects, and conduct pilot trials. The American College of Radiology Imaging Network infrastructure may be suitable for these purposes. There is an extraordinary opportunity for DW-MRI to evolve into a clinically valuable imaging tool, potentially important for drug development.

Normal and transplanted rat kidneys: diffusion MR imaging at 7 T.

To investigate the feasibility of obtaining reproducible apparent diffusion coefficient (ADC) maps of normal rat kidneys by using respiratory-triggered spin-echo diffusion-weighted magnetic resonance (MR) imaging, to investigate the sensitivity of ADC maps in the evaluation of renal blood flow, and to use this technique to monitor acute graft rejection in transplanted rat kidneys. Spin-echo diffusion-weighted MR imaging measurements were performed in 20 normal rats and nine rats that had undergone transplantation (six rats had received allografts; three had received isografts) at 7 T. To evaluate the effect of alteration in blood flow and water transport function, angiotensin II was infused in six normal rats and a series of spin-echo diffusion-weighted MR images was obtained at five time points. Transplanted kidneys were monitored by obtaining spin-echo diffusion-weighted MR images and gradient-echo MR images every 2 hours for 8 hours on postoperative day 4. Statistical analysis was performed with repeated-measures multivariate analysis of variance and the paired t test. No significant differences in ADC values were observed between right and left kidneys in all three orthogonal directions; however, a small difference was observed between the cortex and medulla. ADC values in the cephalocaudal and mediolateral directions were higher than those in the anteroposterior direction (P <.01 for all). ADC values in the cortex and medulla decreased significantly (by >35%, P <.01) during angiotensin II-induced reduction in renal blood flow. No significant signal intensity change was observed between native and transplanted kidneys on gradient-echo MR images. Allografts exhibited decreased ADC values (P <.01) and isografts exhibited similar ADC values compared with native kidneys. These findings suggest that reproducible renal ADC maps can be obtained in rats by using spin-echo diffusion-weighted MR imaging at 7 T. Spin-echo diffusion-weighted MR imaging may have potential as a noninvasive tool for monitoring early graft rejection after kidney transplantation.