Eric A. Mellon

Sodium MR Imaging Detection of Mild Alzheimer Disease: Preliminary Study

BACKGROUND AND PURPOSE: There is significant interest in the development of novel noninvasive techniques for the diagnosis of Alzheimer disease (AD) and tracking its progression. Because MR imaging has detected alterations in sodium levels that correlate with cell death in stroke, we hypothesized that there would be alterations of sodium levels in the brains of patients with AD, related to AD cell death. MATERIALS AND METHODS: A total of 10 volunteers (5 with mild AD and 5 healthy control subjects) were scanned with a 20-minute sodium (23Na) MR imaging protocol on a 3T clinical scanner. RESULTS: After normalizing the signal intensity from the medial temporal lobes corresponding to the hippocampus with the ventricular signal intensity, we were able to detect a 7.5% signal intensity increase in the brains of patients with AD (AD group, 68.25% ± 3.4% vs control group, 60.75% ± 2.9%; P < .01). This signal intensity enhancement inversely correlated with hippocampal volume (AD group, 3.22 ± 0.50 cm3 vs control group, 3.91 ± 0.45 cm3; r2 = 0.50). CONCLUSIONS: This finding suggests that sodium imaging may be a clinically useful tool to detect the neuropathologic changes associated with AD.

Detection of lactate with a hadamard slice selected, selective multiple quantum coherence, chemical shift imaging sequence (HDMD-SelMQC-CSI) on a clinical MRI scanner: Application to tumors and muscle ischemia.

Lactate is an important metabolite in normal and malignant tissues detectable by NMR spectroscopy; however, it has been difficult to clinically detect the lactate methyl resonance because it is obscured by lipid resonances. The selective homonuclear multiple quantum coherence transfer technique offers a method for distinguishing lipid and lactate resonances. We implemented a three‐dimensional selective homonuclear multiple quantum coherence transfer version with Hadamard slice selection and two‐dimensional phase encoding (Hadamard encoded–selective homonuclear multiple quantum coherence transfer–chemical shift imaging) on a conventional clinical MR scanner. Hadamard slice selection is explained and demonstrated in vivo. This is followed by 1‐cm3 resolution lactate imaging with detection to 5‐mM concentration in 20 min on a 3‐T clinical scanner. An analysis of QSel gradient duration and amplitude effects on lactate and lipid signal is presented. To demonstrate clinical feasibility, a 5‐min lactate scan of a patient with a non‐Hodgkins lymphoma in the superficial thigh is reported. The elevated lactate signal coincides with the T2‐weighted image of this tumor. As a test of selective homonuclear multiple quantum coherence transfer sensitivity, a thigh tourniquet was applied to a normal volunteer and an increase in lactate was detected immediately after tourniquet flow constriction. In conclusion, the Hadamard encoded–selective homonuclear multiple quantum coherence transfer–chemical shift imaging sequence is demonstrated on a phantom and in two lipid‐rich, clinically relevant, in vivo conditions. Magn Reson Med, 2009.

Compensation for spin-lock artifacts using an off-resonance rotary echo in T1ρoff-weighted imaging

The origin of image artifacts in an off‐resonance spin‐locking experiment is shown to be imperfections in the excitation flip angle. A pulse sequence for off‐resonance spin locking is implemented that compensates for imperfections in the excitation flip angle through an off‐resonance rotary echo. The off‐resonance rotary echo alternates the frequency offset and phase of the RF transmitter during two spin‐locking pulses of equal duration. The underlying theory is detailed, and MR images demonstrate the effectiveness of the technique in agarose gel phantoms and in in vivo human brain at 3T. Magn Reson Med 57:2–7, 2007.

Mapping of cerebral oxidative metabolism with MRI

Using a T1ρ MRI based indirect detection method, we demonstrate the detection of cerebral oxidative metabolism and its modulation by administration of the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) in a large animal model with minimum utilization of gas. The study was performed by inhalation in swine during imaging on clinical MRI scanners. Metabolic changes in swine were determined by two methods. First, in a series of animals, increased metabolism caused by DNP injection was measured by exhaled gas analysis. The average whole-body metabolic increase in seven swine was 11.9%+/-2.5% per mg/kg, stable over three hours. Secondly, hemispheric brain measurements of oxygen consumption stimulated by DNP injection were made in five swine using T1ρ MRI following administration of gas. Metabolism was calculated from the change in the T1ρ weighted MRI signal due to H217O generated from inhalation before and after doubling of metabolism by DNP. These results were confirmed by direct oxygen-17 MR spectroscopy, a gold standard for in vivo H217O measurement. Overall, this work underscores the ability of indirect oxygen-17 imaging to detect oxygen metabolism in an animal model with a lung capacity comparable to the human with minimal utilization of expensive gas. Given the demonstrated high efficiency in use of and the proven feasibility of performing such measurements on standard clinical MRI scanners, this work enables the adaption of this technique for human studies dealing with a broad array of metabolic derangements.

Measurement of creatine kinase reaction rate in human brain using magnetization transfer image-selected in vivo spectroscopy (MT-ISIS) and a volume 31P/1H radiofrequency coil in a clinical 3-T MRI system

High‐energy phosphate metabolism, which allows the synthesis and regeneration of adenosine triphosphate (ATP), is a vital process for neuronal survival and activity. In particular, creatine kinase (CK) serves as an energy reservoir for the rapid buffering of ATP levels. Altered CK enzyme activity, reflecting compromised high‐energy phosphate metabolism or mitochondrial dysfunction in the brain, can be assessed using magnetization transfer (MT) MRS. MT 31P MRS has been used to measure the forward CK reaction rate in animal and human brain, employing a surface radiofrequency coil. However, long acquisition times and excessive radiofrequency irradiation prevent these methods from being used routinely for clinical evaluations. In this article, a new MT 31P MRS method is presented, which can be practically used to measure the CK forward reaction rate constant in a clinical MRI system employing a volume head 31P coil for spatial localization, without contamination from the scalp muscle, and an acquisition time of 30 min. Other advantages associated with the method include radiofrequency homogeneity within the regions of interest of the brain using a volume coil with image‐selected in vivo spectroscopy localization, and reduction of the specific absorption rate using nonadiabatic radiofrequency pulses for MT saturation. The mean value of kf was measured as 0.320 ± 0.075 s−1 from 10 healthy volunteers with an age range of 18–40 years. These values are consistent with those obtained using earlier methods, and the technique may be used routinely to evaluate energetic processes in the brain on a clinical MRI system. Copyright

Single Shot T1ρ Magnetic Resonance Imaging Of Metabolically Generated Water In Vivo

The use of Oxygen-17 MRI provides great promise for the clinically-useful quantification of metabolism. To bring techniques based on 17O closer to clinical application, we demonstrate imaging of metabolically generated H2 17O in pigs after 17O2 delivery with increased temporal resolution T1rho-weighted imaging and precision delivery of 17O2 gas. The kinetics of the appearance of H2 17O in pig brains are displayed with one to two minutes of 17O2 delivery, the shortest delivery times reported in the literature. It is also shown that H2 17O concentrations can be quantified with single shot T1rho imaging based on a balanced steady state free precession readout, and that with this strategy pausing to reduce T1 saturation increases sensitivity to H2 17O over acquisition in the steady state. Several additional considerations with this sequence, which can be generalized to any pre-encoding cluster, such as energy deposition are considered.

NMR Metabolic and Physiological Markers of Therapeutic Response

Identification of reliable metabolic and physiological NMR detectable markers for prediction and early detection of therapeutic response is essential to enabling NMR guided individualized therapy for cancer. Because non-Hodgkins lymphoma (NHL) is a prevalent form of cancer that exhibits~50% response to therapy and often presents with large superficial lesions easily accessible to multinuclear magnetic resonance spectroscopy (MRS) measurements, it is an ideal test bed for development of NMR methods for prediction and early detection of response.A multicenter study, in which we have participated, has already shown that pre-treatment(31) PMRS measurement of the phosphate monoester (PME)to nucleoside triphosphate (NTP) ratio can identify about 2/3 of the patients who are destined not to exhibit a complete clinical response to a variety of therapeutic agents.Because (31)PMRS is limited to relatively large superficial tumors, we have been exploring (1)HMRS and MRI methods for early detection of therapeutic response. Using xenografts of the most common form of human NHL, diffuse large B-cell lymphoma (DLBCL), we have detected therapeutic response within one cycle of therapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), rituximab plus CHOP (RCHOP) or radiation (15 Gy) through detection of a decrease in lactic acid (Lac) or total choline (tCho) and an increase of apparent diffusion coefficients (ADC). We have also performed (1)H MRS of NHL patients in a clinical scanner. One of the patients exhibited a 70% decrease in Lac within 48 h of treatment with RCHOP.