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One of the most challenging problems in modern neuroimaging is detailed characterization of neurodegeneration. Quantifying spatial and longitudinal atrophy patterns is an important component of this process. These spatiotemporal signals will aid in discriminating between related diseases, such as frontotemporal dementia (FTD) and Alzheimer's disease (AD), which manifest themselves in the same at-risk population. Here, we develop a novel symmetric image normalization method (SyN) for maximizing the cross-correlation within the space of diffeomorphic maps and provide the Euler-Lagrange equations necessary for this optimization. We then turn to a careful evaluation of our method. Our evaluation uses gold standard, human cortical segmentation to contrast SyN's performance with a related elastic method and with the standard ITK implementation of Thirion's Demons algorithm. The new method compares favorably with both approaches, in particular when the distance between the template brain and the target brain is large. We then report the correlation of volumes gained by algorithmic cortical labelings of FTD and control subjects with those gained by the manual rater. This comparison shows that, of the three methods tested, SyN's volume measurements are the most strongly correlated with volume measurements gained by expert labeling. This study indicates that SyN, with cross-correlation, is a reliable method for normalizing and making anatomical measurements in volumetric MRI of patients and at-risk elderly individuals.

We introduce a simple, efficient, low-SAR method for magnetic resonance imaging in the presence of a static field with a permanent, and possibly large gradient. The technique, which is called slant-slice imaging is essentially a spin-echo imaging sequence except that the imaging slice is oriented such that the static field gradient can be used in conjunction with applied gradients during readout. Data are collected for 2D slices. Unlike single point imaging techniques, entire lines of k-space are acquired with each readout. The slant-slice pulse sequence is used to obtain high quality images, using a clinical scanner to simulate a static field with a large permanent gradient. The effects of the inhomogeneity are quantified by two parameters nu and q, which are useful for assessing the utility of a magnet design for 3D-MR imaging.

Susceptibility artifacts due to metallic prostheses are a major problem in clinical magnetic resonance imaging. We theoretically and experimentally analyze slice distortion arising from susceptibility differences in a phantom consisting of a stainless steel ball bearing embedded in agarose gel. To relate the observed image artifacts to slice distortion, we simulate images produced by 2D and 3D spin-echo (SE) and a view angle tilting (VAT) sequence. Two-dimensional SE sequences suffer from extreme slice distortion when a metal prosthesis is present, unlike 3D SE sequences for which--since slices are phase-encoded--distortion of the slice profile is minimized, provided the selected slab is larger than the region of interest. In a VAT sequence, artifacts are reduced by the application of a gradient along the slice direction during readout. However, VAT does not correct for the excitation slice profile, which results in the excitation of spins outside the desired slice location and can lead to incorrect anatomical information in MR images. We propose that the best sequences for imaging in the presence of a metal prosthesis utilize 3D acquisition, with phase encoding replacing slice selection to minimize slice distortion, combined with excitation and readout gradient strengths at their maximum values.

This paper provides the practical details required to use the inverse scattering (IST) approach to design selective RF-pulses. As in the Shinnar-Le Roux (SLR) approach, we use a hard pulse approximation to actually design the pulse. Unlike SLR, the pulse is designed using the full inverse scattering data (the reflection coefficient and the bound states) rather than the flip angle profile. We explain how to approximate the reflection coefficient to obtain a pulse with a prescribed rephasing time. In contrast to the SLR approach, we retain direct control on the phase of the magnetization profile throughout the design process. We give explicit recursive algorithms for computing the hard pulse from the inverse scattering data. These algorithms are quite different from the SLR recursion, being essentially discretizations of the Marchenko equations. We call our approach the discrete inverse scattering transform or DIST. Overall, it is as fast as the SLR approach. When bound states are present, we use both the left and right Marchenko equations to improve the numerical stability of the algorithm. We compute a variety of examples and consider the effect of amplitude errors on the magnetization profile.

In a paper of Nielson et al. it is shown, using the linear approximation, that it might be possible to create a pair of RF-pulses, which, after summation of the unrephased signals achieve a specified transverse magnetization. Such pulses, designed using the linear approximation, show rather poor slice selectivity. Using the inverse scattering transform formalism we give an algorithm to exactly achieve a specified "summed" transverse magnetization profile. Indeed for a constant phase transverse profile, our algorithm produces infinitely many solutions.

This paper considers a variety of problems in the design of selective RF-pulses. We apply a formula of Zakharov and Manakov to directly relate the energy of an RF-envelope to the magnetization profile and certain auxiliary parameters used in the inverse scattering transform (IST) approach to RF-pulse synthesis. This allows a determination of the minimum possible energy for a given magnetization profile. We give an algorithm to construct both the minimum energy RF-envelope as well as any other envelope that produces a given magnetization profile. This includes an algorithm for solving the Gel'fand-Levitan-Marchenko equations with bound states. The SLR method is analyzed in terms of traditional scattering data, and shown to be a special (singular) case of the IST approach. RF-envelopes are computed for a variety of examples.

Anti-B-blocked ricin (anti-B4-bR) combines the specificity of the anti-B4 (CD19) monoclonal antibody with the protein toxin "blocked ricin." In blocked ricin, affinity ligands are attached to the ricin B-chain to attenuate its lectin binding capacity. In a phase I trial, Anti-B4-bR was administered by 7-day continuous infusion to 12 patients in complete remission after autologous bone marrow transplantation (ABMT) for relapsed B-cell non-Hodgkin's lymphoma (NHL). Patients were treated at 20, 40, and 50 micrograms/kg/d for 7 days. Potentially therapeutic serum levels could be sustained for 3 to 4 days. The maximum tolerated dose was 40 micrograms/kg/d for 7 days (total 280 micrograms/kg). The dose-limiting toxicities were reversible grade IV thrombocytopenia and elevation of hepatic transaminases. Mild capillary leak syndrome was manifested by hypoalbuminemia, peripheral edema (4 patients), and dyspnea (1 patient). Anti-immunotoxin antibodies developed in 7 patients. Eleven patients remain in complete remission between 13 and 26 months post-ABMT (median 17 months). These results show that Anti-B4-bR can be administered with tolerable, reversible toxicities to patients with B-cell NHL in complete remission following ABMT.