Carolyn E. Mountford

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.

Organization of lipids in the plasma membranes of malignant and stimulated cells: a new model

Neutral lipids make up about 6% of the lipid content of plasma membranes from malignant cells. Magnetic resonance spectroscopy (MRS) identifies this neutral lipid as predominantly triglyceride which is not in bilayer form. A new structural model is proposed whereby neutral lipid domains are intercalated with the bilayer lipid of the plasma membrane. A functional role for these neutral lipid domains is also proposed based on plasma membrane alterations which occur with cellular stimulation, with the acquisition of resistance to anti-cancer drugs, and in metastatic cells.

Neurospectroscopy: The Past, Present and Future

Neurospectroscopy with respect to its past, present and future has been reported. It is helpful to understand the biochemical relevance of each of the major resonances in the brain spectra. Lactate is seen in the spectrum as a doublet at 1.33 ppm. Healthy tissues do not have sufficient lactate to be detectable by MRS. Neurospectroscopy provides information on brain constituents. Pattern recognition blends pattern recognition techniques and multivariate statistical analysis with solid, comprehensive software engineering practices. Neurospectroscopy offers a window into the chemistry of the human brain, reporting on normal mechanisms as well as the changes that occur with degeneration, disease, pain, cancer, and infection. Alzheimers disease can now be identified much earlier than before offering earlier management before the disease progresses. The long-term effect of shaken baby syndrome and traumatic brain injury can be gauged by neurospectroscopy.

Rapid Identification of Candida Species by Using Nuclear Magnetic Resonance Spectroscopy and a Statistical Classification Strategy

ABSTRACT Nuclear magnetic resonance (NMR) spectra were acquired from suspensions of clinically important yeast species of the genus Candida to characterize the relationship between metabolite profiles and species identification. Major metabolites were identified by using two-dimensional correlation NMR spectroscopy. One-dimensional proton NMR spectra were analyzed by using a staged statistical classification strategy. Analysis of NMR spectra from 442 isolates of Candida albicans, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis resulted in rapid, accurate identification when compared with conventional and DNA-based identification. Spectral regions used for the classification of the five yeast species revealed species-specific differences in relative amounts of lipids, trehalose, polyols, and other metabolites. Isolates of C. parapsilosis and C. glabrata with unusual PCR fingerprinting patterns also generated atypical NMR spectra, suggesting the possibility of intraspecies discontinuity. We conclude that NMR spectroscopy combined with a statistical classification strategy is a rapid, nondestructive, and potentially valuable method for identification and chemotaxonomic characterization that may be broadly applicable to fungi and other microorganisms.

In vivo proton MR spectroscopy of the breast.

In vivo proton magnetic resonance (MR) spectroscopy (hydrogen 1 spectroscopy) provides useful information about the pathology of breast lesions by the measurement of diagnostic chemicals visible on the MR timescale. Spectroscopic measurements may be obtained following contrast-enhanced MR imaging by applying a point-resolved spatially localized spectroscopy sequence. The observation of resonances at discrete spectral frequencies allows an accurate diagnosis. In spectra obtained in vivo in malignant breast cancers, an observed resonance at 3.23 ppm is consistent with phosphocholine. In spectra from benign breast lesions and some normal breast tissue in lactating mothers and in some nonlactating healthy women, a recorded resonance at 3.28 ppm is thought to originate from glycerophosphocholine, taurine, or myoinositol. The success of in vivo spectroscopy depends on the appropriate pre-acquisition setup, acquisition protocol, and postprocessing techniques for achieving high spectral resolution and a signal-to-noise ratio sufficient to separate the resonances of the important biomarkers. When implemented correctly, the method is diagnostically accurate and robust.

Spectroscopic imaging with improved gradient modulated constant adiabaticity pulses on high-field clinical scanners.

The purpose of this work was to design and implement constant adiabaticity gradient modulated pulses that have improved slice profiles and reduced artifacts for spectroscopic imaging on 3T clinical scanners equipped with standard hardware. The newly proposed pulses were designed using the gradient offset independent adiabaticity (GOIA, Tannus and Garwood[13]) method using WURST modulation for RF and gradient waveforms. The GOIA-WURST pulses were compared with GOIA-HSn (GOIA based on nth-order hyperbolic secant) and FOCI (frequency offset corrected inversion) pulses of the same bandwidth and duration. Numerical simulations and experimental measurements in phantoms and healthy volunteers are presented. GOIA-WURST pulses provide improved slice profile that have less slice smearing for off-resonance frequencies compared to GOIA-HSn pulses. The peak RF amplitude of GOIA-WURST is much lower (40% less) than FOCI but slightly higher (14.9% more) to GOIA-HSn. The quality of spectra as shown by the analysis of lineshapes, eddy currents artifacts, subcutaneous lipid contamination and SNR is improved for GOIA-WURST. GOIA-WURST pulse tested in this work shows that reliable spectroscopic imaging could be obtained in routine clinical setup and might facilitate the use of clinical spectroscopy.

Proton MRS of the breast in the clinical setting.

Information for determining whether a primary breast lesion is invasive and its receptor status and grade can be obtained before surgery by performing proton MRS on a fine‐needle aspiration biopsy (FNAB) specimen and analyzing the MRS information by a pattern recognition method. Two‐dimensional MRS, on either specimens or cells, allows the unambiguous assignment of most resonances. When correlated with the spectral regions selected by the pattern recognition method, there are strong indications for the biochemical markers responsible for prognostic information of invasive capacity and metastatic spread. Spectral assignments and biological correlations can be made using cell models. In vivo MRS can distinguish invasive from benign lesions. This pathological distinction can be made from the presence of resonances at discrete frequencies. To achieve this level of spectral resolution and signal‐to‐noise ratio, there are stringent requirements when acquiring and processing the data. The challenge now is to implement two‐dimensional MRS in vivo. Until this is realized, the combination of in vivo MR, for diagnosis and spatial location, and MRS, for image‐guided biopsy to provide information on tumor spread, promises to provide a higher level of preoperative diagnosis than previously achieved. Copyright

Magnetic resonance spectroscopy detects biochemical changes in the brain associated with chronic low back pain: a preliminary report

Magnetic resonance (MR) spectroscopy is a noninvasive technique that can be used to detect and measure the concentration of metabolites and neurotransmitters in the brain and other organs. We used in vivo 1H MR spectroscopy in subjects with low back pain compared with control subjects to detect alterations in biochemistry in three brain regions associated with pain processing. A pattern recognition approach was used to determine whether it was possible to discriminate accurately subjects with low back pain from control subjects based on MR spectroscopy. MR spectra were obtained from the prefrontal cortex, anterior cingulate cortex, and thalamus of 32 subjects with low back pain and 33 control subjects without pain. Spectra were analyzed and compared between groups using a pattern recognition method (Statistical Classification Strategy). Using this approach, it was possible to discriminate between subjects with low back pain and control subjects with accuracies of 100%, 99%, and 97% using spectra obtained from the anterior cingulate cortex, thalamus, and prefrontal cortex, respectively. These results demonstrate that MR spectroscopy, in combination with an appropriate pattern recognition approach, is able to detect brain biochemical changes associated with chronic pain with a high degree of accuracy.

CLASSIFICATION OF HUMAN TUMOURS BY HIGH-RESOLUTION MAGNETIC RESONANCE SPECTROSCOPY

Malignant tumours yield a high-resolution proton magnetic resonance (MR) spectrum. Fifty-one tumour biopsy specimens from patients with cancer of the ovary or colon were examined by magnetic resonance spectroscopy (MRS) to determine whether it was possible to identify tumour subtypes with metastatic potential. Relaxation parameters (T2) for visible lipid methylene protons were within the range of those measured for three animal metastasis models. Primary carcinomas with metastases gave T2 values greater than 350 ms, whereas carcinomas not associated with known metastases at the time of tumour excision gave a range of values from 150 to 1500 ms. All but two carcinomas gave a long T2 (greater than 350 ms) indicating metastatic potential. The MRS method designated five of six histologically borderline epithelial ovarian tumours as malignant with metastatic potential. MRS may be sensitive enough to detect malignant cells in a tumour which is of intermediate or borderline malignancy by light microscopy. Malignancy without a potential for metastasis is uncommon.

Tetraphenylphosphonium chloride induced mr‐visible lipid accumulation in a malignant human breast cell line

The effect of the cationic lipophilic phosphonium salt tetraphenylphosphonium chloride (TPP) on a human malignant breast cell line, DU4475, was monitored with proton nuclear magnetic resonance (1H MRS). TPP caused a dose‐ and time‐dependent increase in resonances arising from MR‐visible lipid as measured by the CH2/CH3 ratio in the I‐dimensional 1H MR spectrum. Two‐dimensional MRS identified increases in the glycerophosphocholine/lysine cross‐peak ratio and corresponding decreases in the phosphocholine/lysine ratio in a dose‐dependent fashion in TPP‐treated cells. Lipid metabolic changes are discussed in the light of other MR experiments, and the data indicate that accumulation of MR‐visible lipids may arise from the rearrangement of phospholipids accompanying mitochondrial destruction or from the catabolism of phospholipids associated with early events in the cytotoxic process.