William D. Rooney

Magnetic field and tissue dependencies of human brain longitudinal 1H2O relaxation in vivo

Brain water proton (1H2O) longitudinal relaxation time constants (T1) were obtained from three healthy individuals at magnetic field strengths (B0) of 0.2 Tesla (T), 1.0T, 1.5T, 4.0T, and 7.0T. A 5‐mm midventricular axial slice was sampled using a modified Look‐Locker technique with 1.5 mm in‐plane resolution, and 32 time points post‐adiabatic inversion. The results confirmed that for most brain tissues, T1 values increased by more than a factor of 3 between 0.2T and 7T, and over this range were well fitted by T1 (s) = 0.583(B0)0.382, T1(s) = 0.857(B0)0.376, and T1(s) = 1.35(B0)0.340 for white matter (WM), internal GM, and blood 1H2O, respectively. The ventricular cerebrospinal fluid (CSF) 1H2O T1 value did not change with B0, and its average value (standard deviation (SD)) across subjects and magnetic fields was 4.3 (±0.2) s. The tissue 1/T1 values at each field were well correlated with the macromolecular mass fraction, and to a lesser extent tissue iron content. The field‐dependent increases in 1H2O T1 values more than offset the well‐known decrease in typical MRI contrast reagent (CR) relaxivity, and simulations predict that this leads to lower CR concentration detection thresholds with increased magnetic field. Magn Reson Med 57:308–318, 2007.

Variation of the relaxographic “shutter‐speed” for transcytolemmal water exchange affects the CR bolus‐tracking curve shape

Contrast reagents (CRs) may enter the tissue interstitium for a period after a vascular bolus injection. As the amount of interstitial CR increases, the longitudinal relaxographic NMR “shutter‐speed” (T–1) for the equilibrium transcytolemmal water exchange process increases. The quantity T–1 is given by |r1o[CRo] + R1o0 – R1i| (where r1o and [CRo] represent the interstitial (extracellular) CR relaxivity and concentration, respectively, and R1o0 and R1i are the extra‐ and intracellular 1H2O relaxation rate constants, respectively, in the absence of exchange). The increase of T–1 with [CRo] causes the kinetics of the water exchange equilibrium to appear to decrease. Here, analytical theory for two‐site‐exchange processes is combined with that for pharmacokinetic CR delivery, extraction, and distribution in a method termed BOLus Enhanced Relaxation Overview (BOLERO©). The shutter‐speed effect alters the shape of the bolus‐tracking (B‐T) time‐course. It is shown that this is mostly accounted for by the inclusion of only one additional parameter, which measures the mean intracellular lifetime of a water molecule. Simulated and real data demonstrate that the effect of shutter‐speed variation on pharmacokinetic parameters can be very significant: neglecting this effect can lead to an underestimation of the parameter values by 50%. This phenomenon can be heterogeneous. Within a tiny gliosarcoma implanted in the rat brain, the interstitial CR in the tumor core never rises to a level sufficient to cause apparent slowing of the exchange process. However, within the few microns needed to reach the proliferating rim, this occurs to a significant degree. Thus, even relative pharmacokinetic quantities can be incorrectly represented in a parametric map that neglects this effect. The BOLERO analysis shows promise for in vivo vascular phenotyping in pathophysiology. It also includes a provision for approximating the separation of the perfusion and permeability contributions to CR extravasation. Magn Reson Med 50:1151–1169, 2003.

Decreased N‐acetylaspartate in motor cortex and corticospinal tract in ALS

The primary objectives of this study were to test whether 1) N-acetylaspartate (NAA), a neuronal marker, is reduced in motor cortex and corticospinal-tract (CST) brain regions of ALS patients; and 2) motor cortex NAA correlates to a clinical measurement of upper motor neuron function in ALS patients. Ten probable or definite ALS patients and nine neurologically normal control subjects were studied. Three axial planes of two-dimensional 1H MRSI data were collected, using a single spin-echo multislice sequence (TE140/TR2000). Two of the 1H MRSI planes were positioned superior to the lateral ventricles, and one plane was positioned at the level of the internal capsule. Spectroscopy voxels were selected from motor cortex, frontal cortex, parietal cortex, medial gray matter, centrum semiovale white matter, anterior internal capsule, and posterior internal capsule. Peak integrals were obtained for the three major 1H MRSI singlet resonances, NAA, creatine and phosphocreatine (Cr), and cholines (Cho). Maximum finger-tap rate was used as a clinical measurement of upper motor neuron function. In ALS, brain NAAl(Cho+Cr) was reduced 19% (p = 0.024) in the motor cortex and 16% (p = 0.021) in the CST (centrum semiovale and posterior internal capsule) regions. NAA/ (Cho+Cr) was not reduced in frontal cortex, parietal cortex, medial gray matter, or anterior internal capsule. There was a significant relation between ALS motor cortex NAA/(Cho+Cr) and maximum finger-tap rate (r = 0.80; p = 0.014). NAA/(Cho+Cr) was reduced in motor cortex and CST regions and unchanged in other brain regions of ALS patients when compared with controls. These findings are consistent with the known distribution of neuronal loss in ALS. The positive correlation between motor cortex NAA/(Cho+Cr) and maximum finger-tap rate suggests that reduced NAA/(Cho+Cr) is a surrogate marker of motor cortex neuron loss in ALS. These findings support the study of 1H MRSI NAA measurement as an objective and quantitative measurement of upper motor neuron dysfunction in ALS.

Shutter-speed analysis of contrast reagent bolus-tracking data: Preliminary observations in benign and malignant breast disease

The standard pharmacokinetic model applied to contrast reagent (CR) bolus‐tracking (B‐T) MRI (dynamic‐contrast‐enhanced) data makes the intrinsic assumption that equilibrium transcytolemmal water molecule exchange is effectively infinitely fast. Theory and simulation have suggested that this assumption can lead to significant errors. Recent analyses of animal model experimental data have confirmed two predicted signature inadequacies: a specific temporal mismatch with the B‐T time‐course and a CR dose‐dependent underestimation of model parameters. The most parsimonious adjustment to account for this aspect leads to the “shutter‐speed” pharmacokinetic model. Application of the latter to the animal model data mostly eliminates the two signature inadequacies. Here, the standard and shutter‐speed models are applied to B‐T data obtained from routine human breast examinations. The signature standard model temporal mismatch is found for each of the three invasive ductal carcinoma (IDC) cases and for each of the three fibroadenoma (FA) cases studied. It is effectively eliminated by use of the shutter‐speed model. The size of the mismatch is considerably greater for the IDC lesions than for the FA lesions, causing the shutter‐speed model to exhibit improved discrimination of malignant IDC tumors from the benign FA lesions compared with the standard model. Furthermore, the shutter‐speed model clearly reveals focal “hot spots” of elevated CR perfusion/permeation present in only the malignant tumors. Magn Reson Med 53:724–729, 2005.

Reduced MTR in the corticospinal tract and normal T2 in amyotrophic lateral sclerosis

The objective of this study was to test the hypothesis that magnetization transfer ratios (MTR) are decreased in the corticospinal tract of patients with amyotrophic lateral sclerosis (ALS); to determine if T2 is increased in corticospinal tract or reduced in motor cortex in ALS; to determine if corticospinal tract MTR correlates with a clinical measure of motor neuron function in ALS. Ten ALS patients and 17 age-matched controls were studied. Double spin echo MRI and 3D gradient echo MRI with and without off-resonance saturation were acquired on each subject. 3D data sets were coregistered and resliced to match the spin echo data set. MTR was calculated for corticospinal and non-corticospinal tract white matter. T2 was calculated for corticospinal and non-corticospinal tract white matter, motor cortex and non-motor cortex. MTR was reduced by 2.6% (p < .02) in corticospinal, but not in non-corticospinal, tract white matter in ALS. There was no difference in T2 in any brain region. The correlation between a clinical measure of motor neuron function and corticospinal tract MTR was statistically significant. These findings are consistent with the known pathology in ALS and suggest that MTR is more sensitive than T2 for detecting involvement of the corticospinal tract. Quantitative MTR of the corticospinal tract may be a useful, objective marker of upper motor neuron pathology in ALS.

Reanalysis of multislice 1h MRSI in amyotrophic lateral sclerosis

The goal of this work was to reexamine previously published (1) brain spectroscopy data of abnormal metabolite ratios in amyotrophic lateral sclerosis (ALS). Toward this goal, 1H MR spectroscopic imaging data from 10 ALS and nine control subjects were reanalyzed using improved data analysis techniques, including automated curve fitting and tissue‐volume correction. In the motor cortex of ALS, N‐acetyl aspartate (NAA) was 23% (P = 0.004) lower than in controls, and in the posterior internal capsule of ALS choline compounds (Cho) were 20% (P = 0.02) higher. This demonstrates that the metabolite ratio changes in ALS were due to NAA loss in the motor cortex (as expected) and Cho increase in the posterior internal capsule (not expected). Magn Reson Med 45:513–516, 2001.

Development of a simultaneous PET/MRI scanner

A combined magnetic resonance imaging (MRI) and positron emission tomography (PET) scanner would be a great benefit to nuclear medicine. The anatomical detail given by MRI and spectroscopy available with magnetic resonance spectroscopy (MRS) complement the quantitative physiological imaging obtained with PET. Such a device has not become a reality because of the incompatibilities of photomultiplier tubes (PMTs) and their associated electronics with MRIs high magnetic fields, as well as significant constraints on PET camera size due to the limited patient port of MR scanners. Recent advances in solid-state electronics have opened the possibility of replacing photomultiplier tubes with avalanche photodiodes (APDs) that are compact and do not share the vulnerabilities of PMTs to magnetic fields. Currently, we are planning to build a miniature PET tomograph using only solid-state electronics to give a combination MRI/PET scanner for small animals. This technology, once developed, can be extended to human scanner designs.

Cell Membrane Water Exchange Effects in Prostate DCE-MRI

Prostate Dynamic-Contrast-Enhanced (DCE) MRI often exhibits fast and extensive global contrast reagent (CR) extravasation - measured by K(trans), a pharmacokinetic parameter proportional to its rate. This implies that the CR concentration [CR] is high in the extracellular, extravascular space (EES) during a large portion of the DCE-MRI study. Since CR is detected indirectly, through water proton signal change, the effects of equilibrium transcytolemmal water exchange may be significant in the data and thus should be admitted in DCE-MRI pharmacokinetic modeling. The implications for parameter values were investigated through simulations, and analyses of actual prostate data, with different models. Model parameter correlation and precision were also explored. A near-optimal version of the exchange-sensitized model was found. Our results indicate that ΔK(trans) (the K(trans) difference returned by this version and a model assuming exchange to be effectively infinitely fast) may be a very useful biomarker for discriminating malignant from benign prostate tissue. Using an exchange-sensitized model, we find that the mean intracellular water lifetime (τ(i)) - an exchange measure - can be meaningfully mapped for the prostate. Our results show prostate glandular zone differences in τ(i) values.

Intimate combination of low‐ and high‐resolution image data: I. real‐space PET and 1H2O MRI, PETAMRI

Two different types of (co‐registered) images of the same slice of tissue will generally have different spatial resolutions. The judicious pixel‐by‐pixel combination of their data can be accomplished to yield a single image exhibiting properties of both. Here, axial 18FDG PET and 1H2O MR images of the human brain are used as the low‐ and high‐resolution members of the pair. A color scale is necessary in order to provide for separate intensity parameters from the two image types. However, not all color scales can accommodate this separability. The HSV color model allows one to choose a color scale in which the intensity of the low‐resolution image type is coded as hue, while that of the high‐resolution type is coded as value, a reasonably independent parameter. Furthermore, the high‐resolution image must have high contrast and be quantitative in the same sense as the low‐resolution image almost always is. Here, relaxographic MR images (naturally segmented quantitative 1H2O spin‐density components) are used. Their essentially complete contrast serves to effect an apparent editing function when encoded as the value of the color scale. Thus, the combination of 18FDG PET images with gray‐matter (GM) relaxographic 1H2O images produces visually “GM‐edited” 18FDG PETAMR (positron emission tomography and magnetic resonance) images. These exhibit the high sensitivity to tracer amounts characteristic of PET along with the high spatial resolution of 1H2O MRI. At the same time, however, they retain the complete quantitative measures of each of their basis images. Magn Reson Med 42:345–360, 1999. Published 1999 Wiley‐Liss, Inc.

Preliminary Studies of a Simultaneous PET/MRI Scanner Based on the RatCAP Small Animal Tomograph

We are developing a scanner that will allow the simultaneous acquisition of high resolution anatomical data using magnetic resonance imaging (MRI) and quantitative physiological data using positron emission tomography (PET). The approach is based on the technology used for the RatCAP conscious small animal PET tomograph which utilizes block detectors consisting of pixelated arrays of LSO crystals read out with matching arrays of avalanche photodiodes (APDs) and a custom-designed ASIC. A version of the detector is being developed that will be constructed out of all nonmagnetic materials that can be operated inside the MRI field. We have demonstrated that the PET detector works inside the MRI field using 511 keV gamma rays, and have obtained MRI images with various detector components that show minimal distortion in the MRI image. We plan to improve on the image quality in the future using completely nonmagnetic components and by tuning the MRI pulse sequences. The combined result will be a highly compact, low mass PET scanner that can operate inside an MRI magnet without distorting the MRI image, and can be retrofitted into existing MRI instruments.