Extracranial applications of diffusion-weighted magnetic resonance imaging

Diffusion-weighted MRI has become more and more popular in the last couple of years. It is already an accepted diagnostic tool for patients with acute stroke, but is more difficult to use for extracranial applications due to technical challenges mostly related to motion sensitivity and susceptibility variations (e.g., respiration and air-tissue boundaries). However, thanks to the newer technical developments, applications of body DW-MRI are starting to emerge. In this review, we aim to provide an overview of the current status of the published data on DW-MRI in extracranial applications. A short introduction to the physical background of this promising technique is provided, followed by the current status, subdivided into three main topics, the functional evaluation, tissue characterization and therapy monitoring.

Cerebral connectivity and psychotic personality traits : A diffusion tensor imaging study

This study aims to investigate the relationship between regional connectivity in the brain white matter and the presence of psychotic personality traits, in healthy subjects with psychotic traits. Thirteen healthy controls were administered the MMPI-2, to assess psychotic traits and, according to MMPI results, a dichotomization into a group of "high-psychotic" and "low-psychotic" was performed. Diffusion tensor imaging (DTI) was used as a non-invasive measure, in order to obtain information about the fractional anisotropy (FA), an intravoxel index of local connectivity and, by means of a voxelwise approach, the between-group differences of the FA values were calculated. The "high-psychotic" group showed higher FA in the left arcuate fasciculus. Subjects with low scores for psychotic traits had significantly higher FA in the corpus callosum, right arcuate fasciculus, and fronto-parietal fibers. In line with previous brain imaging studies of schizophrenia spectrum disorders, our results suggest that psychotic personality traits are related to altered connectivity and brain asymmetry.

Characterization of white matter alterations in phenylketonuria by magnetic resonance relaxometry and diffusion tensor imaging

A multimodal MR study including relaxometry, diffusion tensor imaging (DTI), and MR spectroscopy was performed on patients with classical phenylketonuria (PKU) and matched controls, to improve our understanding of white matter (WM) lesions. Relaxometry yields information on myelin loss or malformation and may substantiate results from DTI attributed to myelin changes. Relaxometry was used to determine four brain compartments in normal-appearing brain tissue (NABT) and in lesions: water in myelin bilayers (myelin water, MW), water in gray matter (GM), water in WM, and water with long relaxation times (cerebrospinal fluid [CSF]-like signals). DTI yielded apparent diffusion coefficients (ADCs) and fractional anisotropies. MW and WM content were reduced in NABT and in lesions of PKU patients, while CSF-like signals were significantly increased. ADC values were reduced in PKU lesions, but also in the corpus callosum. Diffusion anisotropy was reduced in lesions because of a stronger decrease in the longitudinal than in the transverse diffusion. WM content and CSF-like components in lesions correlated with anisotropy and ADC. ADC values in lesions and in the corpus callosum correlated negatively with blood and brain phenylalanine (Phe) concentrations. Intramyelinic edema combined with vacuolization is a likely cause of the WM alterations. Correlations between diffusivity and Phe concentrations confirm vulnerability of WM to high Phe concentrations.

Periprocedural embolic events related to carotid artery stenting detected by diffusion-weighted MRI: comparison between proximal and distal embolus protection devices

PURPOSE: To evaluate and compare the efficacy of proximal versus distal embolus protection devices (EPD) during carotid artery angioplasty/stenting (CAS) based on diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: Forty-four patients (31 men; mean age 68 years, range 48-85) underwent protected CAS and had DW-MRI before and after the intervention. The cohort was analyzed according to the type of EPD used: a proximal EPD was deployed in 25 (56.8%) patients (17 men; mean age 66 years, range 48-85) and a distal filter in 19 (14 men; mean age 70 years, range 58-79). Fifteen (60.0%) patients with proximal protection were symptomatic of the target lesion; in the distal protection group, 10 (52.6%) were symptomatic. RESULTS: New lesions were seen on the postinterventional DW-MRI in 28.0% (7/25) of the proximal EPD group versus 32.6% (6/19) of those with a distal filter (p = NS). The majority were clinically silent. The new lesions in the vascular territory of the stented carotid artery in the group as a whole and per patient were fewer in the proximal EPD group (p = NS). No significant differences were noted in the T(2) appearance of the new lesions or the number of new lesions observed away from the vascular territory of the stented artery. CONCLUSION: Proximal embolus protection devices show a nonsignificant trend toward fewer embolic events, which warrants large-scale studies. Furthermore, proximal protection devices can be useful to control and treat acute in-stent thrombosis.

Contribution of the apparent diffusion coefficient in perilesional edema for the assessment of brain tumors

OBJECTIVES: Diffusion-weighted MRI is sensitive to molecular motion and has been applied to the diagnosis of stroke. Our intention was to investigate its usefulness in patients with brain tumor and, in particular, in the perilesional edema. METHODS: We performed MRI of the brain, including diffusion-weighted imaging and mapping of the apparent diffusion coefficient (ADC), in 16 patients with brain tumors (glioblastomas, low-grade gliomas and metastases). ADC values were determined by the use of regions of interest positioned in areas of high signal intensities as seen on T2-weighted images and ADC maps. Measurements were taken in the tumor itself, in the area of perilesional edema and in the healthy contralateral brain. RESULTS: ADC mapping showed higher values of peritumoral edema in patients with glioblastoma (1.75 x 10(-3)mm(2)/s) and metastatic lesions (1.61 x 10(-3)mm(2)/s) compared with those who had low-grade glioma (1.40 x10(-3)mm(2)/s). The higher ADC values in the peritumoral zone were associated with lower ADC values in the tumor itself. CONCLUSIONS: The higher ADC values in the more malignant tumors probably reflect vasogenic edema, thereby allowing their differentiation from other lesions.

Steady-state diffusion imaging for MR in-vivo evaluation of reparative cartilage after matrix-associated autologous chondrocyte transplantation at 3 tesla--preliminary results

OBJECTIVES: To demonstrate the feasibility of time-reversed fast imaging with steady-state precession (FISP) called PSIF for diffusion-weighted imaging of cartilage and cartilage transplants in a clinical study. MATERIAL AND METHODS: In a cross-sectional study 15 patients underwent MRI using a 3D partially balanced steady-state gradient echo pulse sequence with and without diffusion weighting at two different time points after matrix-associated autologous cartilage transplantation (MACT). Mean diffusion quotients (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) within the cartilage transplants were compared to diffusion quotients found in normal cartilage. RESULTS: The global diffusion quotient found in repair cartilage was significantly higher than diffusion values in normal cartilage (p<0.05). There was a decrease between the earlier and the later time point after surgery. CONCLUSIONS: In-vivo diffusion-weighted imaging based on the PSIF technique is possible. Our preliminary results show follow-up of cartilage transplant maturation in patients may provide additional information to morphological assessment.

Prostate carcinoma: diffusion-weighted imaging as potential alternative to conventional MR and 11C-choline PET/CT for detection of bone metastases

In a technical development study approved by the institutional ethics committee, the feasibility of fast diffusion-weighted imaging as a replacement for conventional magnetic resonance (MR) imaging sequences (short inversion time inversion recovery [STIR] and T1-weighted spin echo [SE]) and positron emission tomography (PET)/computed tomography (CT) in the detection of skeletal metastases from prostate cancer was evaluated. MR imaging and carbon 11 ((11)C) choline PET/CT data from 11 consecutive prostate cancer patients with bone metastases were analyzed. Diffusion-weighted imaging appears to be equal, if not superior, to STIR and T1-weighted SE sequences and equally as effective as (11)C-choline PET/CT in detection of bone metastases in these patients. Diffusion-weighted imaging should be considered for further evaluation and comparisons with PET/CT for comprehensive whole-body staging and restaging in prostate and other cancers.

Diffusion tensor imaging of two unrelated Chinese men with hereditary spastic paraplegia associated with thin corpus callosum

Hereditary spastic paraplegia (HSP) associated with thin corpus callosum is a rare autosomal recessive neurodegenerative disorder characterized by an abnormally thin corpus callosum, normal motor development, slowly progressive spastic paraparesis and cognitive deterioration. To investigate and localize abnormalities in the brains of two Chinese patients with HSP-TCC, with mutations in the spatacsin gene. Diffusion tensor imaging (DTI) was used to determine the mean diffusion (MD) and fractional anisotropy (FA) in the brains of the patients in comparison to 20 healthy subjects. Voxel-based analysis (VBA) of both the diffusion and anisotropy values were performed using statistical parametric mapping (SPM). Significant changes with MD increase and FA reduction were found in the already known lesions including the corpus callosum, cerebellum and thalamus. In addition, changes were also found in regions that appear to be normal in conventional MRI, such as the brain stem, internal capsule, cingulum and subcortical white matter including superior longitudinal fascicle and inferior longitudinal fascicle. Neither increase in FA nor reduction in MD was detected in the brain. Our study provides clear in vivo MR imaging evidence of a more widespread brain involvement of HSP-TCC. MD is more sensitive than FA in detecting lesions in thalamus and subcortical white matter, suggesting that MD may be a better marker of the disease progression.

Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging reliably detect pelvic lymph node metastases in normal-sized nodes of bladder and prostate cancer patients

BACKGROUND: Lymph node staging of bladder or prostate cancer using conventional imaging is limited. Newer approaches such as ultrasmall superparamagnetic particles of iron oxide (USPIO) and diffusion-weighted magnetic resonance imaging (DW-MRI) have inconsistent diagnostic accuracy and are difficult to interpret. OBJECTIVE: To assess whether combined USPIO and DW-MRI (USPIO-DW-MRI) improves staging of normal-sized lymph nodes in bladder and/or prostate cancer patients. DESIGN, SETTING, AND PARTICIPANTS: Twenty-one consecutive patients with bladder and/or prostate cancer were enrolled between May and October 2008. One patient was excluded secondary to bone metastases detected on DW-MRI with subsequent abstention from surgery. INTERVENTION: Patients preoperatively underwent 3-T MRI before and after administration of lymphotropic USPIO using conventional MRI sequences combined with DW-MRI. Surgery consisted of extended pelvic lymphadenectomy and resection of primary tumors. MEASUREMENTS: Diagnostic accuracies of the new combined USPIO-DW-MRI approach compared with the "classic" reading method evaluating USPIO images without and with DW-MRI versus histopathology were evaluated. Duration of the two reading methods was noted for each patient. RESULTS AND LIMITATIONS: Diagnostic accuracy (90% per patient or per pelvic side) was comparable for the classic and the USPIO-DW-MRI reading method, while time of analysis with 80 min (range 45-180 min) for the classic and 13 min (range 5-90 min) for the USPIO-DW-MRI method was significantly shorter (p<0.0001). Interobserver agreement (three blinded readers) was high with a kappa value of 0.75 and 0.84, respectively. Histopathological analysis showed metastases in 26 of 802 analyzed lymph nodes (3.2%). Of these, 24 nodes (92%) were correctly diagnosed as positive on USPIO-DW-MRI. In two patients, one micrometastasis each (1.0x0.2 mm; 0.7x0.4 mm) was missed in all imaging studies. CONCLUSIONS: USPIO-DW-MRI is a fast and accurate method for detecting pelvic lymph node metastases, even in normal-sized nodes of bladder or prostate cancer patients.

Multimodal approach in the use of clinical scoring, morphological MRI and biochemical T2-mapping and diffusion-weighted imaging in their ability to assess differences between cartilage repair tissue after microfracture therapy and matrix-associated autologous chondrocyte transplantation: a pilot study

OBJECTIVE: The aim of the present pilot study is to show initial results of a multimodal approach using clinical scoring, morphological magnetic resonance imaging (MRI) and biochemical T2-relaxation and diffusion-weighted imaging (DWI) in their ability to assess differences between cartilage repair tissue after microfracture therapy (MFX) and matrix-associated autologous chondrocyte transplantation (MACT). METHOD: Twenty patients were cross-sectionally evaluated at different post-operative intervals from 12 to 63 months after MFX and 12-59 months after MACT. The two groups were matched by age (MFX: 36.0+/-10.4 years; MACT: 35.1+/-7.7 years) and post-operative interval (MFX: 32.6+/-16.7 months; MACT: 31.7+/-18.3 months). After clinical evaluation using the Lysholm score, 3T-MRI was performed obtaining the MR observation of cartilage repair tissue (MOCART) score as well as T2-mapping and DWI for multi-parametric MRI. Quantitative T2-relaxation was achieved using a multi-echo spin-echo sequence; semi-quantitative diffusion-quotient (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) was prepared by a partially balanced, steady-state gradient-echo pulse sequence. RESULTS: No differences in Lysholm (P=0.420) or MOCART (P=0.209) score were observed between MFX and MACT. T2-mapping showed lower T2 values after MFX compared to MACT (P=0.039). DWI distinguished between healthy cartilage and cartilage repair tissue in both procedures (MFX: P=0.001; MACT: P=0.007). Correlations were found between the Lysholm and the MOCART score (Pearson: 0.484; P=0.031), between the Lysholm score and DWI (Pearson:-0.557; P=0.011) and a trend between the Lysholm score and T2 (Person: 0.304; P=0.193). CONCLUSION: Using T2-mapping and DWI, additional information could be gained compared to clinical scoring or morphological MRI. In combination clinical, MR-morphological and MR-biochemical parameters can be seen as a promising multimodal tool in the follow-up of cartilage repair.

Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging

PURPOSE: To compare dynamic contrast material-enhanced magnetic resonance (MR) imaging and diffusion-weighted MR imaging for noninvasive evaluation of early and late effects of a vascular targeting agent in a rat tumor model. MATERIALS AND METHODS: The study protocol was approved by the local ethics committee for animal care and use. Thirteen rats with one rhabdomyosarcoma in each flank (26 tumors) underwent dynamic contrast-enhanced imaging and diffusion-weighted echo-planar imaging in a 1.5-T MR unit before intraperitoneal injection of combretastatin A4 phosphate and at early (1 and 6 hours) and later (2 and 9 days) follow-up examinations after the injection. Histopathologic examination was performed at each time point. The apparent diffusion coefficient (ADC) of each tumor was calculated separately on the basis of diffusion-weighted images obtained with low b gradient values (ADC(low); b = 0, 50, and 100 sec/mm(2)) and high b gradient values (ADC(high); b = 500, 750, and 1000 sec/mm(2)). The difference between ADC(low) and ADC(high) was used as a surrogate measure of tissue perfusion (ADC(low) - ADC(high) = ADC(perf)). From the dynamic contrast-enhanced MR images, the volume transfer constant k and the initial slope of the contrast enhancement-time curve were calculated. For statistical analyses, a paired two-tailed Student t test and linear regression analysis were used. RESULTS: Early after administration of combretastatin, all perfusion-related parameters (k, initial slope, and ADC(perf)) decreased significantly (P < .001); at 9 days after combretastatin administration, they increased significantly (P < .001). Changes in ADC(perf) were correlated with changes in k (R(2) = 0.46, P < .001) and the initial slope (R(2) = 0.67, P < .001). CONCLUSION: Both dynamic contrast-enhanced MR imaging and diffusion-weighted MR imaging allow monitoring of perfusion changes induced by vascular targeting agents in tumors. Diffusion-weighted imaging provides additional information about intratumoral cell viability versus necrosis after administration of combretastatin.