Roland Bammer

Basic principles of diffusion-weighted imaging

In diffusion-weighted MRI (DWI), image contrast is determined by the random microscopic motion of water protons. During the last years, DWI has become an important modality in the diagnostic work-up of acute ischemia in the CNS. There are also a few promising reports about the application of DWI to other regions in the human body, such as the vertebral column or the abdomen. This manuscript provides an introduction into the basics of DWI and Diffusion Tensor imaging. The potential of various MR sequences in concert with diffusion preparation are discussed with respect to acquisition speed, spatial resolution, and sensitivity to bulk physiologic motion. More advanced diffusion measurement techniques, such as high angular resolution diffusion imaging, are also addressed.

Diffusion tensor imaging using single-shot SENSE-EPI.

SENSitivity Encoding (SENSE) greatly enhances the quality of diffusion‐weighted echo‐planar imaging (EPI) by reducing blurring and off‐resonance artifacts. Such improvement would also be desirable for diffusion tensor imaging (DTI), but measures derived from the diffusion tensor can be extremely sensitive to any kind of image distortion. Whether DTI is feasible in combination with SENSE has not yet been explored, and is the focus of this study. Using a SENSE‐reduction factor of 2, DTI scans in eight healthy volunteers were carried out with regular‐ and high‐resolution acquisition matrices. To further improve the stability of the SENSE reconstruction, a new coil‐sensitivity estimation technique based on variational calculus and the principles of matrix regularization was applied. With SENSE, maps of the trace of the diffusion tensor and of fractional anisotropy (FA) had improved spatial resolution and less geometric distortion. Overall, the geometric distortions were substantially removed and a significant resolution enhancement was achieved with almost the same scan time as regular EPI. DTI was even possible without the use of quadrature body coil (QBC) reference scans. Geometry‐factor‐related noise enhancement was only discernible in maps generated with higher‐resolution matrices. Error boundaries for residual fluctuations in SENSE reconstructions are discussed. Our results suggest that SENSE can be combined with DTI and may present an important adjunct for future neuroimaging applications of this technique. Magn Reson Med 48:128–136, 2002.

Children's reading performance is correlated with white matter structure measured by diffusion tensor imaging

We investigated the white matter structure in children (n = 14) with a wide range of reading performance levels using diffusion tensor imaging (DTI), a form of magnetic resonance imaging. White matter structure in a left temporo-parietal region that had been previously described as covarying with reading skill in adult readers also differs between children who are normal and poor readers. Specifically, the white matter structure measured using fractional anisotropy (FA) and coherence index (CI) significantly correlated with behavioral measurements of reading, spelling, and rapid naming performance. In general, lower anisotropy and lower coherence were associated with lower performance scores. Although the magnitude of the differences in children are smaller than those in adults, the results support the hypothesis that the structure of left temporoparietal neural pathways is a significant component of the neural system needed to develop fluent reading.

COGNITIVE PROCESSING SPEED AND THE STRUCTURE OF WHITE MATTER PATHWAYS: CONVERGENT EVIDENCE FROM NORMAL VARIATION AND LESION STUDIES

We investigated the relation between cognitive processing speed and structural properties of white matter pathways via convergent imaging studies in healthy and brain-injured groups. Voxel-based morphometry (VBM) was applied to diffusion tensor imaging data from thirty-nine young healthy subjects in order to investigate the relation between processing speed, as assessed with the Digit-Symbol subtest from WAIS-III, and fractional anisotropy, an index of microstructural organization of white matter. Digit-Symbol performance was positively correlated with fractional anisotropy of white matter in the parietal and temporal lobes bilaterally and in the left middle frontal gyrus. Fiber tractography indicated that these regions are consistent with the trajectories of the superior and inferior longitudinal fasciculi. In a second investigation, we assessed the effect of white matter damage on processing speed using voxel-based lesion-symptom mapping (VLSM) analysis of data from seventy-two patients with left-hemisphere strokes. Lesions in left parietal white matter, together with cortical lesions in supramarginal and angular gyri were associated with impaired performance. These findings suggest that cognitive processing speed, as assessed by the Digit-Symbol test, is closely related to the structural integrity of white matter tracts associated with parietal and temporal cortices and left middle frontal gyrus. Further, fiber tractography applied to VBM results and the patient findings suggest that the superior longitudinal fasciculus, a major tract subserving fronto-parietal integration, makes a prominent contribution to processing speed.

Improved diffusion-weighted single-shot echo-planar imaging (EPI) in stroke using sensitivity encoding (SENSE)

Diffusion‐weighted single‐shot EPI (sshEPI) is one of the most important tools for the diagnostic assessment of stroke patients, but it suffers from well known artifacts. Therefore, sshEPI was combined with SENSitivity Encoding (SENSE) to further increase EPIs potential for stroke imaging. Eight healthy volunteers and a consecutive series of patients (N = 8) with suspected stroke were examined with diffusion‐weighted SENSE‐sshEPI using different reduction factors (1.0 ≤ R ≤ 3.0). Additionally, a high‐resolution diffusion‐weighted SENSE‐sshEPI scan was included. All examinations were diagnostic and of better quality than conventional sshEPI. No ghostings or aliasing artifacts were discernible, and EPI‐related image distortions were markedly diminished. Chemical shift artifacts and eddy current‐induced image warping were still present, although to a markedly smaller extent. Measured direction‐dependent diffusion‐coefficients and isotropic diffusion values were comparable to previous findings but showed less fluctuation. We have demonstrated the technical feasibility and clinical applicability of diffusion‐weighted SENSE‐sshEPI in patients with subacute stroke. Because of the faster k‐space traversal, this novel technique is able to reduce typical EPI artifacts and increase spatial resolution while simultaneously remaining insensitive to bulk motion. Magn Reson Med 46:548–554, 2001.

Magnetic resonance diffusion tensor imaging for characterizing diffuse and focal white matter abnormalities in multiple sclerosis

High‐resolution diffusion tensor imaging (DTI) was performed in 14 patients with clinically definite multiple sclerosis (MS) and the trace of the diffusion tensor (〈D〉) and the fractional anisotropy (FA) were determined in normal appearing white matter (NAWM) and in different types of focal MS lesions. A small but significant increase of the 〈D〉 in NAWM compared to control white matter ((840 ± 85) × 10–6 mm2/sec vs. (812 ± 59) × 10–6 mm2/sec; P < 0.01) was found. In addition, there was a significant decrease in the FA of normal‐appearing regions containing well‐defined white matter tracts, such as the genu of the internal capsule. In non‐acute lesions, the 〈D〉 of T1‐hypointense areas was significantly higher than that of T1‐isointense lesions ((1198 ± 248) × 10–6 mm2/sec vs. (1006 ± 142) × 10–6 mm2/sec; P < 0.001), and there was a corresponding inverse relation of FA. Diffusion characteristics of active lesions with different enhancement patterns were also significantly different. DTI with a phase navigated interleaved echo planar imaging technique may be used to detect abnormalities of isotropic and anisotropic diffusion in the NAWM and selected fiber tracts of patients with MS throughout the entire brain, and it demonstrates substantial differences between various types of focal lesions. Magn Reson Med 44:583–591, 2000.

Optimal Tmax Threshold for Predicting Penumbral Tissue in Acute Stroke

Background and Purpose— We sought to assess whether the volume of the ischemic penumbra can be estimated more accurately by altering the threshold selected for defining perfusion-weighting imaging (PWI) lesions. Methods— DEFUSE is a multicenter study in which consecutive acute stroke patients were treated with intravenous tissue-type plasminogen activator 3 to 6 hours after stroke onset. Magnetic resonance imaging scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Baseline and posttreatment PWI volumes were defined according to increasing Tmax delay thresholds (>2, >4, >6, and >8 seconds). Penumbra salvage was defined as the difference between the baseline PWI lesion and the final infarct volume (30-day fluid-attenuated inversion recovery sequence). We hypothesized that the optimal PWI threshold would provide the strongest correlations between penumbra salvage volumes and various clinical and imaging-based outcomes. Results— Thirty-three patients met the inclusion criteria. The correlation between infarct growth and penumbra salvage volume was significantly better for PWI lesions defined by Tmax >6 seconds versus Tmax >2 seconds, as was the difference in median penumbra salvage volume in patients with a favorable versus an unfavorable clinical response. Among patients who did not experience early reperfusion, the Tmax >4 seconds threshold provided a more accurate prediction of final infarct volume than the >2 seconds threshold. Conclusions— Defining PWI lesions based on a stricter Tmax threshold than the standard >2 seconds delay appears to provide more a reliable estimate of the volume of the ischemic penumbra in stroke patients imaged between 3 and 6 hours after symptom onset. A threshold between 4 and 6 seconds appears optimal for early identification of critically hypoperfused tissue.

Diffusion MRI in multiple sclerosis

Diffusion imaging is a quantitative, MR-based technique potentially useful for the study of multiple sclerosis (MS), due to its increased pathologic specificity over conventional MRI and its ability to assess in vivo the presence of tissue damage occurring outside T2-visible lesions, i.e., in the so-called normal-appearing white and gray matter. The present review aims at critically summarizing the state-of-the-art and providing a background for the planning of future diffusion studies of MS. Several pieces of evidence suggest that diffusion-weighted and diffusion tensor MRI are sensitive to MS damage and able to detect its evolution over relatively short periods of time. Although a significant relationship between diffusion-weighted MRI findings and MS clinical disability was not found in the earliest studies, with improved diffusion imaging technology correlations between diffusion abnormalities and MS clinical aspects are now emerging. However, the best acquisition and postprocessing strategies for MS studies remain a matter of debate and the contribution of newer and more sophisticated techniques to diffusion tensor MRI investigations in MS needs to be further evaluated. Although changes in diffusion MRI indices reflect a net loss of structural organization, at present we can only speculate on their possible pathologic substrates in the MS brain. Postmortem studies correlating diffusion findings with histopathology of patients with MS are, therefore, also warranted.

Characterizing non-Gaussian diffusion by using generalized diffusion tensors.

Diffusion tensor imaging (DTI) is known to have a limited capability of resolving multiple fiber orientations within one voxel. This is mainly because the probability density function (PDF) for random spin displacement is non‐Gaussian in the confining environment of biological tissues and, thus, the modeling of self‐diffusion by a second‐order tensor breaks down. The statistical property of a non‐Gaussian diffusion process is characterized via the higher‐order tensor (HOT) coefficients by reconstructing the PDF of the random spin displacement. Those HOT coefficients can be determined by combining a series of complex diffusion‐weighted measurements. The signal equation for an MR diffusion experiment was investigated theoretically by generalizing Ficks law to a higher‐order partial differential equation (PDE) obtained via Kramers‐Moyal expansion. A relationship has been derived between the HOT coefficients of the PDE and the higher‐order cumulants of the random spin displacement. Monte‐Carlo simulations of diffusion in a restricted environment with different geometrical shapes were performed, and the strengths and weaknesses of both HOT and established diffusion analysis techniques were investigated. The generalized diffusion tensor formalism is capable of accurately resolving the underlying spin displacement for complex geometrical structures, of which neither conventional DTI nor diffusion‐weighted imaging at high angular resolution (HARD) is capable. The HOT method helps illuminate some of the restrictions that are characteristic of these other methods. Furthermore, a direct relationship between HOT and q‐space is also established. Magn Reson Med 51:924–937, 2004.

Real-time Diffusion-Perfusion Mismatch Analysis in Acute Stroke

Diffusion‐perfusion mismatch can be used to identify acute stroke patients that could benefit from reperfusion therapies. Early assessment of the mismatch facilitates necessary diagnosis and treatment decisions in acute stroke. We developed the RApid processing of PerfusIon and Diffusion (RAPID) for unsupervised, fully automated processing of perfusion and diffusion data for the purpose of expedited routine clinical assessment. The RAPID system computes quantitative perfusion maps (cerebral blood volume, CBV; cerebral blood flow, CBF; mean transit time, MTT; and the time until the residue function reaches its peak, Tmax) using deconvolution of tissue and arterial signals. Diffusion‐weighted imaging/perfusion‐weighted imaging (DWI/PWI) mismatch is automatically determined using infarct core segmentation of ADC maps and perfusion deficits segmented from Tmax maps. The performance of RAPID was evaluated on 63 acute stroke cases, in which diffusion and perfusion lesion volumes were outlined by both a human reader and the RAPID system. The correlation of outlined lesion volumes obtained from both methods was r2 = 0.99 for DWI and r2 = 0.96 for PWI. For mismatch identification, RAPID showed 100% sensitivity and 91% specificity. The mismatch information is made available on the hospitals PACS within 5–7 min. Results indicate that the automated system is sufficiently accurate and fast enough to be used for routine care as well as in clinical trials. J. Magn. Reson. Imaging 2010;32:1024–1037.