Biomedical subjects

O Gonen

Publications and source records attributed to O Gonen.

At least 19 recordsLinked to original sources

PubMed2007

Reproducibility of the whole-brain N-acetylaspartate level across institutions, MR scanners, and field strengths.

BACKGROUND AND PURPOSE: Radiologic markers in multicenter trials are often confounded by different instrumentation used. Our goal was to estimate the variance of the global concentration of the neuronal cell marker N-acetylaspartate (NAA) among research centers using MR imaging scanners of different models, from different manufacturers, and of different magnetic field strength. MATERIALS AND METHODS: Absolute millimolar amounts of whole-brain NAA (WBNAA) were quantified with nonlocalizing proton MR spectroscopy in the brains of 101 healthy subjects (53 women, 48 men) aged 16-59 years (mean, 34.2 years). Twenty-three were scanned at 1 institute in a 1.5T Siemens Vision; 31 from another institute were studied with a 1.5T Siemens SP63; 36 were scanned at a third institute (24 with a 1.5T Vision, 12 with a 3T Siemens Trio); and 11 were obtained at a fourth institute using a 4T GE Signa 5.x. The NAA amounts were quantified with phantom-replacement and divided by the brain volume, segmented from MR imaging, to yield the concentration, a metric independent of brain size suitable for cross-sectional comparison. RESULTS: The average WBNAA concentration among institutions was 12.2 +/- 1.2 mmol/L. The subjects' WBNAA distributions did not differ significantly (p > .237) among the 4 centers, regardless of scanner manufacturer, model, or field strength and irrespective of whether adjustments were made for age or sex. CONCLUSION: Absolute quantification against a standard makes the WBNAA concentration insensitive to the MR hardware used to acquire it. This important attribute renders it a robust surrogate marker for multicenter neurologic trials.

Adolescent↗

PubMed2006

Field, coil, and echo-time influence on sensitivity and reproducibility of brain proton MR spectroscopy.

BACKGROUND AND PURPOSE: Clinical MR imaging scanners now offer many choices of hardware configurations that were not available in the first 25 years of their existence. Our goal was to assess the influence of coil technology, magnetic field strength, and echo time (TE) on the sensitivity, reflected by the signal intensity-to-noise-ratio (SNR) and reproducibility of proton MR spectroscopy (1H-MR spectroscopy). MATERIAL AND METHODS: The SNR, the intersubject reproducibility, and the intrasubject reproducibility of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were compared at the common TEs of 30, 144, and 288 ms, by using 1H-MR spectroscopy in 6 volunteers at (1) 3T with a single-element quadrature (SEQ); (2) 1.5T with SEQ; and (3) 1.5T with a 12-channel phased-array (PA) head coil. RESULTS: In terms of sensitivity, the best SNR for all metabolites was obtained at the shortest TE (30 ms). It was comparable between the 3 and 1.5T with the PA, but approximately 35% better than the 1.5T with SEQ. This SNR difference declined <25% at TE of 144 ms and to equity among all imagers at TE of 288 ms. Reproducibility, reflected in the coefficient of variation (CV), was best for NAA at TE of 288 ms, 15%-50% better than at TE of 30 ms in either gray (GM) or white matter (WM). The CV for Cr was best, at TE of 288 ms for GM, but its WM results were independent of TE. Metabolite level reproducibility did not depend on coil technology or magnetic field strength. CONCLUSIONS: For the same coil type, the SNR of all major metabolites was approximately 35% better at 3T than at 1.5T. This advantage, however, was offset at 1.5T with a PA coil, making it a cost-effective upgrade for existing scanners. Surprisingly and counterintuitively, despite the lowest SNR, the best reproducibility was obtained at the longest TE (288 ms), regardless of field or coil.

Adult↗

PubMed2004

Three-dimensional proton spectroscopy of deep gray matter nuclei in relapsing-remitting MS.

The metabolic changes in the deep gray matter (GM) nuclei, thalamus, and basal ganglia of patients with relapsing-remitting multiple sclerosis were investigated with quantitative, multivoxel, three-dimensional proton MR spectroscopy. This technique facilitated the study of several bilateral structures in a single session at sub-cubic centimeter spatial resolution. Compared with 9 matched control subjects, the deep GM nuclei of 11 patients showed 7% lower N-acetylaspartate and 14% higher choline levels (p = 0.02 for both).

Adult↗

PubMed2004

Neuronal cell injury precedes brain atrophy in multiple sclerosis.

Global brain atrophy estimated using MRI and whole brain N-acetylaspartate (WBNAA) concentration measured with proton MR spectroscopy were obtained in 42 patients with relapsing-remitting multiple sclerosis and 41 matched control subjects. Patients exhibited cross-sectional atrophy (0.5%; p = 0.033) and WBNAA decline (1.8%/y; p = 0.005) vs disease duration. The 3.6-fold rate disparity between the two processes suggests that neuronal/axonal dysfunction (N-acetylaspartate decline) precedes parenchyma loss, not its consequence (i.e., is an earlier, more sensitive specific metric of the ongoing disease activity).

Adult↗

PubMed2003

Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis.

Although axonal pathology is recognized as one of the major pathological features of multiple sclerosis, it is less clear how early in its course it occurs and how it correlates with MRI-visible lesion loads. To assess this early axonal pathology, we quantified the concentration of whole-brain N-acetylaspartate (WBNAA) in a group of patients at the earliest clinical stage of the disease and compared the results with those from healthy controls. Conventional brain MRI and WBNAA using unlocalized proton magnetic resonance spectroscopy were obtained from 31 patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis and paraclinical evidence of dissemination in space, and from 16 matched controls. An additional conventional MRI scan was obtained in all patients 4-6 months later to detect dissemination of lesions in time. The mean WBNAA concentration was significantly lower in patients compared with the controls (P < 0.0001). It was not significantly different between patients with and without enhancing lesions at the baseline MRI or between patients with and without lesion dissemination in time. No correlation was found between WBNAA concentrations and lesion volumes. Widespread axonal pathology, largely independent of MRI-visible inflammation and too extensive to be completely reversible, occurs in patients even at the earliest clinical stage of multiple sclerosis. This finding lessens the validity of the current concept that the axonal pathology of multiple sclerosis is the end-stage result of repeated inflammatory events, and argues strongly in favour of early neuroprotective intervention.

Adult↗

PubMed2001

SNR versus resolution in 3D 1H MRS of the human brain at high magnetic fields.

It is commonly accepted that the signal-to-noise ratio (SNR = peak-signal/RMS-noise) per-unit-time of proton MR spectroscopy (1H-MRS) is linearly proportional to the voxel volume. Consequently, with a headcoil and 30-min acquisition, 1 cm3 is considered the SNR-limited spatial resolution barrier in the human brain. However, since local linewidths, Delta(upsilon*) = (piT2*)(-1), at high magnetic fields (B0), are dominated by regional inhomogeneities (DeltaB0), i.e., T2* << T2, reducing the voxel dimensions may increase T2*. This could compensate, in part, for signal loss with volume decrease. It is shown that for two cubic voxels of sides l1 and l2, l1 > l2, as the volume decreases by (l1/l2)3, their SNR ratio is reduced by only (l1/l2)2 due to a commensurate T2* increase of l1/l2. This is demonstrated in a phantom and the brains of volunteers, with 3D 1H-MRS in a headcoil at 4 T. It is shown that while the cubic voxels' dimensions were all halved, reducing their volume eightfold, their metabolites' SNR decreased only fourfold, due to their Delta(upsilon*s') twofold decrease. In other words, both spatial and spectral resolutions were doubled at a significantly, x2, smaller-than-expected SNR loss. This advantage was exploited to produce quality high spatial resolution, 0.75 x 0.75 x 0.75 cm3, metabolic maps in a 27-min acquisition.

Adult↗

PubMed2001

Quantifying radiation therapy-induced brain injury with whole-brain proton MR spectroscopy: initial observations.

PURPOSE: To quantify the extent of neuronal cell loss imparted to the brain by means of radiation therapy through the decline of the amino acid derivative N-acetylaspartate (NAA) by using proton (hydrogen 1) magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Proton MR spectroscopy in a clinical MR imager was used to ascertain the amount of whole-brain NAA before and immediately after whole-brain radiation therapy 3-4 weeks later. Eight patients (four women, four men; median age, 55 years; age range, 39-70 years) were studied. All subjects had lung cancer (non-small cell lung cancer [n = 5], small-cell lung cancer [n = 3]) and received either palliative or prophylactic whole-brain radiation therapy. Six of them also underwent a Mini-Mental Status Examination (MMSE) for correlation with the whole-brain NAA. Two-tailed Student t tests were used to evaluate the data. RESULTS: A significant (P = .042) average decline in whole-brain NAA of -0.91 mmol per person was observed in the cohort. No corresponding changes occurred in MMSE scores. There was no significant difference in whole-brain NAA decline between prophylactic and therapeutic whole-brain radiation therapy. CONCLUSION: Since whole-brain NAA loss was detected even when MMSE scores were unchanged, the former seems to be a more sensitive measure of radiation therapy injury than is the latter.

Adult↗

PubMed2001

Multivoxel 3D proton spectroscopy in the brain at 1.5 versus 3.0 T: signal-to-noise ratio and resolution comparison.

BACKGROUND AND PURPOSE: The new 3.0-T imagers theoretically yield double the signal-to-noise ratio (SNR) and spectral resolution of 1.5-T instruments. To assess the possible improvements for multivoxel 3D proton MR spectroscopy (1H-MRS) in the human brain, we compared the SNR and spectral resolution performance with both field strengths. METHODS: Three-dimensional 1H-MRS was performed in four 21-29-year-old subjects at 1.5 and 3.0 T. In each, a volume of interest of 9 x 9 x 3 cm was obtained within a field of view of 16 x 16 x 3 cm that was partitioned into four (0.75-cm-thick) 16 x 16-voxel sections, yielding 324 (0.75-cm3) signal voxels per examination. RESULTS: In an acquisition protocol of approximately 27 min, average voxel SNRs increased 23-46% at 3.0 versus 1.5 T in the same brain regions of the same subjects. SNRs for N-acetylaspartate, creatine, and choline, respectively, were as follows: 15.3 +/- 4, 8.2 +/- 2.2, and 8.0 +/- 2.0 at 1.5 T and 22.4 +/- 7.0, 10.1 +/- 3.5, and 10.1 +/- 3.6 at 3.0 T. Spectral resolution (metabolite linewidths) were 3.5 +/- 0.5 Hz at 1.5 T versus 6.1 +/- 1.5 Hz at 3.0 T in approximately 900 voxels. Spectral baselines were noticeably flatter at 3.0 T. CONCLUSION: Expected gains in SNR and spectral resolution were not fully realized in a realistic experiment because of intrinsic and controllable factors. However, the 23-46% improvements obtained enable more reliable peak-area estimation and an 1H-MRS acquisition approximately 50% shorter at 3.0 versus 1.5 T.

Adult↗

PubMed2000

Total brain N-acetylaspartate: a new measure of disease load in MS.

OBJECTIVE: To quantitate the extent of neuronal cell loss in MS via the whole brain's N-acetylaspartate (NAA) concentration (WBNAA). METHODS: Because NAA is assumed to be present only in neuronal cell bodies and their axons, we measured WBNAA as a marker for viable neurons in 12 patients (9 women and 3 men, 26 to 53 years of age) suffering from relapsing-remitting (RR) MS for at least 5 years and compared them with 13 age- and sex-matched normal controls. Total brain NAA was determined with proton MR spectroscopy, and WBNAA was obtained by dividing it by the total brain volume, calculated from high resolution MRI. RESULTS: The WBNAA of the RR MS patients was lower than their matched controls (p<0.005). This difference was greater among older than younger subjects. The linear prediction equations of WBNAA with age indicate a faster, x10, decline in the patients, approximately 0.8% per year of age (p = 0.022). CONCLUSION: The age-dependent decrease of whole brain N-acetylaspartate (WBNAA) in the patients suggests that progressive neuronal cell loss is a cardinal feature of this disease. WBNAA offers a quick, highly reproducible measure of disease progression and may be an important marker of treatment efficacy in MS as well as other neurodegenerative diseases.

Adolescent↗

PubMed2000

The accuracy of whole brain N-acetylaspartate quantification.

A non-localizing pulse sequence to quantify the total amount of N-acetylaspartate (NAA) in the whole brain (WBNAA) was introduced recently [Magn. Reson. Med. 40, 684-689 (1998)]. However, it is known that regional magnetic field inhomogeneities, deltaB0s, arising from susceptibility differences at tissue interfaces, shift and broaden local resonances to outside the integration window, leading to an underestimation of the true amount of NAA in the entire brain. To quantify the upper limit of this loss, the whole-head proton MR spectrum (1H-MRS) of the water was integrated over the same frequency width as the NAA. The ratio of this area/total-water-line was 75 +/- 5% in 5 volunteers. The procedure was repeated with the brain-only water peak, obtained by summing signals only from voxels within that organ from a three-dimensional chemical-shift-imaging (3D CSI) set. It indicated that <10% of the water signal loss occurred in the brain. Therefore, by analogy, WBNAA accounts for >90% of that metabolite.

Adult↗

PubMed1999

Three-dimensional multivoxel proton MR spectroscopy of the brain in children with neurofibromatosis type 1.

BACKGROUND AND PURPOSE: Neurofibromatosis type 1 (NF1), the most common autosomal dominant genetic disorder, frequently manifests as focal areas of signal intensity (FASI) on T2-weighted MR images. The purpose of our study was to investigate whether tumor(s), focal areas of signal intensity (FASI), and normal brain can be differentiated by using 3D multivoxel localized proton MR spectroscopy in children with neurofibromatosis type 1 (NF1) disorder. METHODS: Five children with NF1 and two healthy control subjects, all in the 3- to 11-year-old age group, were studied with a new 3D proton MR spectroscopy technique: a hybrid of 1D fourth-order transverse Hadamard spectroscopic imaging and 2D chemical shift imaging. A 3D volume-of-interest (VOI) was image-guided onto the site of the abnormality and identified on three orthogonal images. Proton MR spectroscopy partitioned the VOI into 6 x 6 x 4 (or 8 x 8 x 4) voxels, 1.5 (or 1.0) cm3 each. RESULTS: Simultaneous coverage of the entire VOI yielded good spectral signal-to-noise ratio from 136 (or 256) voxels in 27 minutes. Proton MR spectroscopy indicated that FASI a) are characterized by significantly elevated choline (Cho), reduced creatine (Cr), 2>Cho: Cr>1.3, and near normal N-acetylaspartate (NAA) levels; b) are different from tumors that exhibit Cho:Cr>2 and no NAA; c) have no intrinsic lipid or lactate signal(s); and d) correlate in spatial extent but are more extensive than indicated by MR imaging. CONCLUSION: Three-dimensional multivoxel proton MR spectroscopy reveals distinct metabolic features that differentiate normal, FASI, and tumor regions in the pediatric brain.

Aspartic Acid↗

PubMed1998

3D multivoxel proton spectroscopy of human brain using a hybrid of 8th-order Hadamard encoding with 2D chemical shift imaging.

Multivoxel 3D localized proton spectroscopy using a hybrid of 1D 8th-order transverse Hadamard spectroscopic imaging (HSI) with 2D chemical shift imaging (CSI) is demonstrated in human brain. The spatially selective HSI pulse incorporates naturally into the PRESS sequence (TE = 135 ms), which then both excites an 8 x 8 x 6 cm parallelepiped volume of interest (VOI) and subdivides it into eight slices. The planes of these slices are further partitioned into 16 x 16 voxel arrays using 2D CSI to yield 8 x 8 x 8 voxels within the VOI. Simultaneous 3D coverage yields good voxel signal-to-noise (8, 12, and 22 for choline, creatine, and N-acetylaspartate, respectively) from these 0.75-ml voxels, in approximately 45 min. The high spatial isolation allows localization to within less than 1 cm from the skull without fat contamination.

Adult↗

PubMed1998

Total brain N-acetylaspartate concentration in normal, age-grouped females: quantitation with non-echo proton NMR spectroscopy.

The intra-individual and inter-individual variations of the global N-acetylaspartate (NAA) concentration were measured in a cohort of five 42+/-5 year-old normal females. The total NAA signal from the whole head was obtained with non-localized non-echo proton spectroscopy (1H-MRS) and converted into absolute mole amounts using phantom replacement. Since NAA is assumed to be present only in neurons, its concentration was obtained by dividing these mole amounts with the brains' volume, calculated from high resolution MRI. The key feature of the procedure is its near-complete suppression of the intense subcutaneous and bone marrow lipids' signals, whose chemical shifts neighbor and underlay the NAA. This was achieved by exploiting the lipids' much shorter T1s, compared to that of NAA, for destructive interference of their signals in co-addition following alternating, nonselective 180 degrees inversions. The average global, inter-individual NAA concentration in that group was found to be 10.63 mM with a 95% confidence interval of 10.43-10.82 mM.

Adult↗

PubMed1997

Simultaneous 3D NMR spectroscopy of proton-decoupled fluorine and phosphorus in human liver during 5-fluorouracil chemotherapy.

Simultaneous acquisition of 1H-decoupled 31P and 19F 3D CSI is demonstrated in the liver of a patient undergoing 5-fluorouracil chemotherapy. Both 31P and 19F shared the same voxel size (64 or 27 ml), bi-level 1H-decoupling and 0.35 s TR. The measurements were done in a 1.5 Tesla clinical imager with three radio-frequency (RF) channels and a triple-tuned surface-coil. The overall MRI and MRS examination time was under 90 min. Simultaneous acquisition of 31P and 19F permits localized study of the influence of hepatic metabolism on the uptake and catabolism of fluoropyrimidine drugs without extra measurement time or higher SAR.

Absorption↗

PubMed1997

In vivo phosphorus polarization transfer and decoupling from protons in three-dimensional localized nuclear magnetic resonance spectroscopy of human brain.

Refocused insensitive nucleus enhancement by polarization transfer (RINEPT) from protons (1H) to a J-coupled phosphorus (31P) has been incorporated into three-dimensional (3D) chemical-shift-imaging (CSI) sequence on a clinical imager. The technique is demonstrated on a phantom and in in vivo human brain. The polarization-transfer efficiency (approximately 1.2) is lower than the theoretical maximum of gamma1H/gamma31P approximately 2.4 resulting from 1H-1H homonuclear J couplings of similar magnitude competing with the 1H --> 31P transfer. Nevertheless, compared with direct 31P Ernst-angle excitation, signal gains of up to x1.8 were obtained mainly as a result of T1 differences between 31P and the 1H. Spectral interpretation is simplified by editing out all non-proton-coupled 31P signals. The duration, approximately 50 min, and power deposition, approximately 1 W x kg(-1), make the application suitable for human studies.

Brain↗

PubMed1997

3D localized in vivo 1H spectroscopy of human brain by using a hybrid of 1D-Hadamard with 2D-chemical shift imaging.

We report acquisition of 3D image-guided localized proton spectroscopy (1H-MRS) in the human brain on a standard clinical imager. 3D coverage is achieved with a hybrid of chemical shift imaging (CSI) and transverse Hadamard spectroscopic imaging (HSI). 16 x 16 x 4 arrays of 3.5 and 1 ml voxels were obtained in 27 min. The spatially selective HSI 90 degrees pulses incorporate naturally into a PRESS double spin-echo sequence to subdivide the VOI into four partitions along its short axis. 2D CSI (16 x 16) is performed along the other long axes. Because the hybrid excites the spins in the entire VOI, a square-root-N signal-to-noise-ratio (SNR) gain per given examination time is realized compared with sequentially interleaving N 2D slices. A two-fold gain in sensitivity is demonstrated in the brain for N = 4.

Adult↗

PubMed1997

Induction of labor versus expectant management in macrosomia: a randomized study.

OBJECTIVE: Macrosomia at term is associated with increased maternal and neonatal morbidity, including a higher rate of cesarean delivery and shoulder dystocia. Induction of labor has been suggested as a means to prevent further weight gain and improve outcome. The aim of this study was to determine whether or not induction of labor in these cases improves maternal and neonatal outcome. METHODS: Patients at term with an ultrasonic fetal weight estimation of 4000-4500 g were prospectively randomized into two groups: induction of labor (group D and expectant management (group II). Patients with diabetes, a previous cesarean delivery, or nonvertex presentation were excluded. Outcome variables included mode of delivery, arterial cord pH, presence of shoulder dystocia, brachial plexus injury, clavicular fracture, cephalohematoma, and intraventricular hemorrhage. RESULTS: Of 273 patients who were eligible for the study, 134 were randomized to group I and 139 to group II. Parity, gestational age, and fetal weight estimation were similar in the two groups. The neonates of group II patients were significantly heavier (4132.8 +/- 347.4 versus 4062.8 +/- 306.9 g; P = .024). The rate of cesarean delivery was 19.4% in group I and 21.6% in group II patients (not significant [NS]). Cord pH was similar in both groups. Shoulder dystocia was diagnosed in five group I and six group II patients (NS). None developed brachial plexus injury. There were two cases of mild, transient brachial plexus injury in group II patients without documented shoulder dystocia. Mild intraventricular hemorrhage was diagnosed in three of 44 group I and two of 31 group II neonates evaluated (NS). CONCLUSION: In this prospective, randomized study, induction of labor for suspected macrosomia at term did not decrease the rate of cesarean delivery or reduce neonatal morbidity. Ultrasonic estimation of fetal weight between 4000 and 4500 g should not be considered an indication for induction of labor.

Adult↗

PubMed1996

Heteronuclear multivoxel spectroscopy of in vivo human brain: two-dimensional proton interleaved with three-dimensional 1H-decoupled phosphorus chemical shift imaging.

Multivoxel, heteronuclear interleaved two-dimensional proton and three-dimensional 1H-decoupled 31P CSI of human brain is demonstrated. This method offers efficient use of limited examination time as patient preparation, coil tuning, shimming and imaging are done only once and the CSI data sets from both nuclei are obtained concurrently. Effective interleaving of 31P and 1H is possible due to the shorter T1s of proton brain metabolites, allowing a 1H acquisition cycle to be inserted into each 31P TR. This way, the entire MRS time is available to both nuclei, increasing their SNR per-unit-time by approximately 12% for 31P and approximately 80% for 1H, compared with sequential detection of equal (45-50 min) length. The spectral resolution and SNR of 31P are further increased through bi-level 1H-decoupling and NOE.

Brain↗