In Vivo GABA Detection by Single Pulse Editing with One Shot

Over the past two decades, magnetic resonance spectroscopy with two-shot difference editing has been widely employed to characterize altered levels of GABA, the primary inhibitory neurotransmitter in the brain, in various neuropsychiatric disorders. This conventional technique detects the GABA H4 resonance, making it unsuitable for investigating GABA metabolism. It also suffers from subtraction artifacts, signal loss, and significant contamination by macromolecules. Here, we introduce a single-shot method for detecting GABA H2, effectively overcoming these difficulties. Since GABA turnover initiates at its protonated C2 and unprotonated C1 positions, we demonstrate, for the first time, noninvasive real-time monitoring of GABA metabolism in the human brain, utilizing GABA H2 as a highly sensitive reporter for GABA C2. This new method not only enhances the quantitative measurement of GABA levels but also opens up a new avenue to probe the metabolic processes underlying alterations in GABA levels in patients

Quantification of in vivo transverse relaxation of glutamate in the frontal cortex of human brain by radio frequency pulse-driven longitudinal steady state.

PurposeThe principal excitatory neurotransmitter glutamate plays an important role in many central nervous system disorders. Because glutamate resides predominantly in glutamatergic neurons, its relaxation properties reflect the intracellular environment of glutamatergic neurons. This study developed an improved echo time-independent technique for measuring transverse relaxation time and demonstrated that this radio frequency (RF)-driven longitudinal steady state technique can reliably measure glutamate transverse relaxation in the frontal cortex, where structural and functional abnormalities have been associated with psychiatric symptoms.MethodBloch and Monte Carlo simulations were performed to improve and optimize the RF-driven, longitudinal, steady-state (MARzss) technique to significantly shorten scan time and increase measurement precision. Optimized four-flip angle measurements at 0°,12°, 24°, and 36° with matched repetition time were used in nine human subjects (6F, 3M; 27-49 years old) at 7 Tesla. Longitudinal and transverse relaxation rates for glutamate were measured from a 2 x 2 x 2 cm3 voxel placed in three different brain regions: gray matter-dominated medial prefrontal lobe, white matter-dominated left frontal lobe, and gray matter-dominated occipital lobe.ResultsCompared to the original MARzss technique, the scan time per voxel for measuring glutamate transverse relaxation was shortened by more than 50%. In the medial frontal, left frontal, and occipital voxels, the glutamate T2 was found to be 117.5±12.9 ms (mean ± standard deviation, n = 9), 107.3±12.1 (n = 9), and 124.4±16.6 ms (n = 8), respectively.ConclusionsThe improvements described in this study make the MARZSS technique a viable tool for reliably measuring glutamate relaxation from human subjects in a typical clinical setting. It is expected that this improved technique can be applied to characterize the intracellular environment of glutamatergic neurons in a variety of brain disorders

PET reveals inflammation around calcified Taenia solium granulomas with perilesional edema.

Neurocysticercosis, an infection with the larval form of the tapeworm, Taeniasolium, is the cause of 29% of epilepsy in endemic regions. Epilepsy in this population is mostly associated with calcified granulomas; at the time of seizure recurrence 50% of those with calcifications demonstrate transient surrounding perilesional edema. Whether edema is consequence of the seizure, or a result of host inflammation directed against parasite antigens or other processes is unknown. To investigate whether perilesional edema is due to inflammation, we imaged a marker of neuroinflammation, translocater protein (TSPO), using positron emission tomography (PET) and the selective ligand (11)C-PBR28.In nine patients with perilesional edema, degenerating cyst or both, PET findings were compared to the corresponding magnetic resonance images. Degenerating cysts were also studied because unlike perilesional edema, degenerating cysts are known to have inflammation. In three of the nine patients, changes in (11)C-PBR28 binding were also studied over time. (11)C-PBR28 binding was compared to the contralateral un-affected region.(11)C-PBR28 binding increased by a mean of 13% in perilesional edema or degenerating cysts (P = 0.0005, n = 13 in nine patients). Among these 13 lesions, perilesional edema (n=10) showed a slightly smaller increase of 10% compared to the contralateral side (P = 0.005) than the three degenerating cysts. In five lesions with perilesional edema in which repeated measurements of (11)C-PBR28 binding were done, increased binding lasted for 2-9 months.Increased TSPO in perilesional edema indicates an inflammatory etiology. The long duration of increased TSPO binding after resolution of the original perilesional edema and the pattern of periodic episodes is consistent with intermittent exacerbation from a continued baseline presence of low level inflammation. Novel anti-inflammatory measures may be useful in the prevention or treatment of seizures in this population

Cerebral phosphoester signals measured by 31P magnetic resonance spectroscopy at 3 and 7 Tesla.

Abnormal cell membrane metabolism is associated with many neuropsychiatric disorders. Free phosphomonoesters and phosphodiesters, which can be detected by in vivo 31P magnetic resonance spectroscopy (MRS), are important cell membrane building blocks. However, the quantification of phosphoesters has been highly controversial even in healthy individuals due to overlapping signals from macromolecule membrane phospholipids (MP). In this study, high signal-to-noise ratio (SNR) cerebral 31P MRS spectra were acquired from healthy volunteers at both 3 and 7 Tesla. Our results indicated that, with minimal spectral interference from MP, the [phosphocreatine (PCr)]/[phosphocholine (PC) + glycerophosphocholine (GPC)] ratio measured at 7 Tesla agreed with its value expected from biochemical constraints. In contrast, the 3 Tesla [PCr]/[PC+GPC] ratio obtained using standard spectral fitting procedures was markedly smaller than the 7 Tesla ratio and than the expected value. The analysis suggests that the commonly used spectral model for MP may fail to capture its complex spectral features at 3 Tesla, and that additional prior knowledge is necessary to reliably quantify the phosphoester signals at low magnetic field strengths when spectral overlapping is significant

Positron emission tomography measurement of ¹¹C-PBR28 binding.

<p>In the first six scans including scan 1 of patient 1 shown in Figure 1, ¹¹C-PBR28 binding was measured as total distribution volume, <i>V</i>_T, using Logan plot [12] based on radioactivity measured by the PET scanner (A, closed circles: perilesional edema in left basal ganglia, open circles: contralateral side with normal MRI) and ¹¹C-PBR28 concentration in arterial plasma measured with radio-high performance liquid chromatography (B). Brain activity decreased to half of the peak in about 60 min indicating that none of the participants including this patient was a low affinity binder [14] to ¹¹C-PBR28. Both the analyses using only area under the curve of brain radioactivity (A) and that using both brain (A) and arterial blood data (B) gave the same increase of 14% in ¹¹C-PBR28 binding indicating that arterial blood sampling was unnecessary.</p

MR and PET images of patient 2 who showed a degenerating cyst (arrow).

<p>The patient presented with a seizure 85 days (01/06/2008) before the PET scan on 03/25/2008. On 02/15/2008 when the patient was asymptomatic, MRI scan showed a Gd-enhanced degenerating cyst in right temporal cortex (arrow). On the day of the PET scan (03/25/2008), the Gd-enhanced lesion slightly shrunk, and the PET scan showed increased ¹¹C-PBR28 binding based on Logan plot (21%) and area under the curve (AUC, 17%). The color bar applies to only the PET image on the left side.</p

MR and PET images of patient 1 following a single perilesional edema episode.

<p>Fluid-attenuated inversion recovery (FLAIR) and gadolinium (Gd)-enhanced T1-weighted MR images at three time points and ¹¹C-PBR28 PET images obtained at two time points. Two lesions are seen, the straight arrow points out a calcification with edema in the left basal ganglion and the curved arrow the edema and calcification in the right centrum semiovale. Although perilesional edema resolved by 01/14/2008, ¹¹C-PBR28 PET uptake was still present. PET images show ¹¹C-PBR28 binding in total distribution volume, <i>V</i>_T. The images are reoriented to show the two lesions on the same coronal slice. Images outside of brain parenchyma are masked.</p