Pre-transplantation 31P-magnetic resonance spectroscopy for quality assessment of human pancreatic grafts – A feasibility study

ObjectiveTo investigate the feasibility of using ³¹P-MRS for objective non-invasive quality assessment of human pancreas grafts prior to transplantation or islet isolation.Materials and methodsPancreata from 5 human donors, 3 males and 2 females, aged 49–78 years, with body mass index (BMI) 22–31 kg/m², were included. Pancreata were perfused with histidine-tryptophan-ketoglutarate solution during procurement and stored in hypothermic condition (4 °C) for 21–44 h. During the period of hypothermic storage repeated spectra were obtained for each graft by ³¹P-MRS (1.5 Tesla) to measure the cold ischemia time (CIT) dependent changes of the phosphorous metabolites adenosine triphosphate (ATP), phosphomonoesters (PME), phosphodiesters (PDE) and inorganic phosphate (Pi), in the grafts. Graft temperature was measured immediately before and after MR-examination. Reference spectrum for non-viable tissue was obtained after graft exposure to room temperature.ResultsPME/Pi, PDE/Pi and ATP/Pi spectral intensities ratios decreased with increasing CIT, reflecting the decreased viability of the grafts. PME/Pi ratio was the most discriminatory variable at prolonged CIT. ³¹P-MRS could be performed without significantly increasing graft temperature.Conclusions³¹P-MRS may provide quantitative parameters for evaluating graft viability ex vivo, and is a promising tool for objective non-invasive assessment of the quality of human pancreas grafts prior to transplantation or islet isolation.     

Phosphorus-31 MR spectroscopic imaging (MRSI) of normal and pathological human brains.

The goals of this study were to evaluate 31P MR spectroscopic imaging (MRSI) for clinical studies and to survey potentially significant spatial variations of 31P metabolite signals in normal and pathological human brains. In normal brains, chemical shifts and metabolite ratios corrected for saturation were similar to previous studies using single-volume localization techniques (n = 10; pH = 7.01 +/- 0.02; PCr/Pi = 2.0 +/- 0.4; PCr/ATP = 1.4 +/- 0.2; ATP/Pi = 1.6 +/- 0.2; PCr/PDE = 0.52 +/- 0.06; PCr/PME = 1.3 +/- 0.2; [Mg2+]free = 0.26 +/- 0.02 mM.) In 17 pathological case studies, ratios of 31P metabolite signals between the pathological regions and normal-appearing (usually homologous contralateral) regions were obtained. First, in subacute and chronic infarctions (n = 9) decreased Pi (65 +/- 12%), PCr (38 +/- 6%), ATP (55 +/- 6%), PDE (47 +/- 9%), and total 31P metabolite signals (50 +/- 8%) were observed. Second, regions of decreased total 31P metabolite signals were observed in normal pressure hydrocephalus (NPH, n = 2), glioblastoma (n = 2), temporal lobe epilepsy (n = 2), and transient ischemic attacks (TIAs, n = 2). Third, alkalosis was detected in the NPH periventricular tissue, glioblastoma, epilepsy ipsilateral ictal foci, and chronic infarction regions; acidosis was detected in subacute infarction regions. Fourth, in TIAs with no MRI-detected infarction, regions consistent with transient neurological deficits were detected with decreased Pi, ATP, and total 31P metabolite signals. These results demonstrate an advantage of 31P MRSI over single-volume 31P MRS techniques in that metabolite information is derived simultaneously from multiple regions of brain, including those outside the primary pathological region of interest. These preliminary findings also suggest that abnormal metabolite distributions may be detected in regions that appear normal on MR images.     

Functional magnetic resonance imaging of human renal allografts during the post-transplant period: Preliminary observations

Graft dysfunction is a common occurrence during the first weeks following renal transplantation. The current study was designed to evaluate the potential of renal magnetic resonance (MR) perfusion imaging to differentiate acute allograft rejection (AAR) from acute tubular necrosis (ATN) during the post-transplant period. Twenty-three consecutive patients with clinically suspected ATN and/or AAR and eight consecutive control patients (asymptomatic, serum creatinine concentration < 1.5 mg/dL) underwent MR perfusion imaging of the renal allograft within 64 days after transplantation. Histopathology was obtained in all cases with clinical suspicion of ATN or AAR. Sixty sequential fast gradient-recalled-echo MR images were acquired in each patient after intravenous administration of gadolinium-DTPA (0.1 mmol/kg). Histopathology revealed 6 patients with pure AAR, 4 patients with a combination of AAR and ATN, 12 patients with ATN and 1 patient with normal findings. Kidney graft recipients with normal renal function showed a moderate increase in signal intensity (SI) of the renal cortex and medulla after administration of contrast agent followed by an immediate and short decrease in SI of the medulla (biphasic medullary enhancement pattern). The increase in cortical SI of patients with AAR was significantly smaller (61 ± 4% increase above baseline) than that measured in normal allografts (136 ± 9% increase above baseline) (p < 0.05) and patients with ATN (129 ± 3% increase above baseline) (p < .05). Patients with ATN had a slightly delayed and diminished cortical enhancement and an uniphasic and lesser medullary enhancement pattern compared to that observed in normal allografts (p < 0.05). A close correlation (r = 0.72) was found between serum creatinine concentration levels and changes in SI. Thus, MR imaging results and histopathology were in agreement in 22 of 23 patients (96%). MR perfusion imaging of renal allografts can be used to noninvasively differentiate ATN from AAR during the post-transplant period, and may also be helpful in cases where covert AAR is superimposing ATN during a phase of anuria. Patients with ATN can be separated from normals in the majority of cases as reflected by an uniphasic medullary enhancement pattern.     

鼠S180肉瘤的体内31P MRS研究

利用表面线圈³¹P NMR研究了小鼠S180肉瘤生长过程中能量代谢和磷脂类变化的特点.结果发现:随着肿瘤体积的增大,(1)Pi和PME升高;(2)PCr降低,在肿瘤体积较大时常检测不到;(3)β-NTP(通常用来表示ATP的量)变化较小;(4)PDE波动性较大;(5)PCr/Pi和β-NTP/Pi比值均下降,且PCr/Pi比β-NTP/Pi下降得快;(6)PME/β-NTP比值升高;(7)肿瘤pH下降,且与PCr/Pi、β-NTP/Pi或(PCr+β-NTP)/Pi比值有相关性.讨论了与这些参数变化相关联的生物学意义.     

Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients

External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Student's t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage.     

Study of B0-->rho+/- pi-/+ time-dependent CP violation at Belle

We present a time-dependent analysis of CP violation in B0-->rho(+/-)pi(-/+) decays based on a 140 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at KEKB. We obtain the charge asymmetry A(rhopi)(CP)=-0.16+/-0.10(stat)+/-0.02(syst). An unbinned maximum-likelihood fit to the Deltat distributions yields C(rhopi)=0.25+/-0.17(stat)+0.02-0.06(syst), DeltaC(rhopi)=0.38+/-0.18(stat)+0.02-0.04(syst), S(rhopi)=-0.28+/-0.23(stat)+0.10-0.08(syst), and DeltaS(rhopi)=-0.30+/-0.24(stat)+/-0.09(syst). The direct CP violation parameters for B-->rho(+)pi(-) and B-->rho(-)pi(+) decays are A(+-)(rhopi)=-0.02+/-0.16(stat)+0.05-0.02(syst) and A(-+)(rhopi)=-0.53+/-0.29(stat)+0.09-0.04(syst).     

光谱法研究2-(4-二甲氨基苯基)-5-氟-6-吗啉-1-氢-苯并咪唑与小牛胸腺DNA的相互作用

研究了2-(4-二甲氨基苯基)-5-氟-6-吗啉-1-氢-苯并咪唑(1)在不同pH条件下的紫外-可见吸收光谱,采用非线性最小二乘法得出分子1的三级加质子常数lgβ₁, lgβ₂, lgβ₃分别为4.96±0.03, 5.72±0.07和7.95±0.10。当pH 3.40时,分子1主要以一价离子状态存在,紫外-可见吸收光谱及荧光光谱表明该条件下分子与小牛胸腺DNA存在明显的相互作用,并得出分子1与DNA的结合常数K_b为(2.30±0.10)×104 mol-1·L。当分子浓度为10-8～1.2×10-6 mol·L-1时,荧光强度随DNA含量的增加而线性增强,分子1是一种潜在的测定DNA的定量试剂。     

Measurements of extracellular volume fraction and capillary permeability in tissues using dynamic spin-lattice relaxometry: studies in rabbit muscles

Dynamic MR longitudinal R(1) relaxometry after administration of a gadolinium contrast bolus (Gd-DTPA) has been used for in vivo measurements of the extracellular volume fraction (v) and the capillary permeability (k min(-1)) in rabbit muscles to distinguish between red slow- and white fast-twitch muscle fiber types. For this purpose a protocol imaging sequence has been used which allows fast R(1) measurements during the contrast agent uptake. Physiological tissue parameters, k and v, were obtained by computing procedures assuming a simplified monoexponential plasma model. These were shown to be about twice as large in the slow-twitch semimembranosous proprius muscle (SP), containing 100% oxidative type-I fiber, that in the fast-twitch rectus femorus muscle (RF), containing only 6% type-I fiber type. The capillary permeability has been found to be 0.25 +/- 0.02 min(-1) for the (SP) and 0.10 +/- 0.01 min(-1) for the (RF). Similarly, the extracellular volume fractions were 0.189 +/- 0.015 and 0.082 +/- 0.006 respectively, in close agreement with literature data and experimental results obtained by invasive radionuclide measurements. For the pool of the 10 studied animals, no significant variation among animals was observed in the extracellular volume fraction and the capillary permeability for the different muscle fiber types. The dynamic relaxometry method used is easy to implement on conventional MR imagers and has potential applications in muscle diseases. The method has also potential applications for tissue characterization based on extracellular volume and capillary permeability quantification. In particular, the method can be used for the evaluation of tumors and their responses to therapies.     

Changes in the liver parenchyma after proton beam radiotherapy: evaluation with MR imaging

The objective of this study was to describe magnetic resonance (MR) findings with a 1.5T imager for hepatic parenchymal changes after proton beam radiotherapy. Thirty-two patients who received proton radiotherapy with doses of 50-87 Gy underwent MR imaging 1-75 months (mean 22 months) after the start of irradiation. Axial T(2), T(1)-weighted imaging, and a dynamic study after a gadolinium injection were performed. The irradiated areas showed hypointense in T(1)-weighted images, hyperintense in T(2)-weighted images, and intense and prolonged enhancement on the dynamic study (maximum relative enhancement 441.8%+/-263.3 vs. surrounding liver 145.6%+/-67.7, p<0.0001). T(2) values of the irradiated areas were 50.6 to 65.8 msec greater than in the surrounding liver (p<0.005). The values increased with time, being significantly greater 13 months or longer after the beginning of the therapy than after a period of less than 3 months (p<0.05). Pathologic examinations (n = 3) indicated that the irradiated areas were composed of collapsed lobules with hepatic small vein occlusions, and rich extracellular matrices which retained extracellular fluid. MR imaging can demonstrate hepatic parenchymal changes after proton beam radiotherapy, and show the changes are irreversible.     

Observation of CP violation in B --> eta'K0 decays

We present measurements of the time-dependent CP-violation parameters S and C in B(0) --> eta(')K(0) decays. The data sample corresponds to 384 x 10(6) BB pairs produced by e(+)e(-) annihilation at the Upsilon(4S). The results are S=0.58+/-0.10+/-0.03 and C=-0.16+/-0.07+/-0.03. We observe mixing-induced CP violation with a significance of 5.5 standard deviations in this b --> s penguin dominated mode.     

Measurement of the lifetime difference in the B0(s) system

We present a study of the decay B0(s) --> J/psiphi. We obtain the CP-odd fraction in the final state at time zero, Rperpendicular = 0.16 +/- 0.10(stat) +/- 0.02 (syst), the average lifetime of the (B0(s), B0(s)) system, tau(B0(s)) = 1.39(+0.13)(-0.16)(stat)(+0.01)(-0.02)(syst) ps, and the relative width difference between the heavy and light mass eigenstates, DeltaGamma/Gamma tripple bond (GammaL - GammaH)/Gamma = 0.24(+0.28)(-0.38)(stat)(+0.03)(-0.04)(syst). With the additional constraint from the world average of the lifetime measurements using semileptonic decays, we find tau(B0(s)) = 1.39 +/- 0.06 ps and DeltaGamma/Gamma = 0.25(+0.14)(-0.15). For the ratio of the B0(s) and B0 lifetimes we obtain tau(B0(s))/tau(B0) = 0.91 +/- 0.09(stat) +/- 0.003(syst).     

Observations of energy metabolism in neuroectodermal tumors using in vivo 31P-NMR

The energy metabolism of living tumors in rats and hamsters were investigated by obtaining in vivo 31P-NMR spectra, and the effects of chemotherapy on tumors were evaluated by observing the changes of these spectra. Tumor cells of rat glioma, human glioblastoma and human neuroblastoma were inoculated subcutaneously in the lumbar region of the animals. After the tumor grew to over 1.5 cm in diameter, in vivo 31P-NMR spectrum data was obtained selectively from the tumor with a TMR-32 spectrometer (Oxford Research Systems, U.K.). Several peaks (ATP, inorganic phosphate (Pi), phosphodiesters and phosphomonoesters (PME) were observed in the tumors. The heights of these peaks varied widely corresponding to the tumor growth. However, the spectrum pattern of each tumor in an active stage was found to be essentially the same regardless of histological type or tumor origin. The phosphocreatine (PCr) peak was small, ATP and PME peaks were large and tissue pH calculated from the chemical shift of Pi was low in each tumor group. After intravenous injection of a large dose of a chemotherapeutic agent, ATP peaks decreased and the Pi peak increased gradually, resulting in a dominant Pi peak pattern after several hours in all groups. With lower drug doses, spectrum changes were temporarily seen in the tumors. These findings indicated that drugs with a high dose have a selective and a direct action on the energy metabolism of tumor tissues. In vivo 31P-NMR spectra measurement is very valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy on the tumor.     

Observation of B Meson decays to b1pi and b1K

We present the results of searches for decays of B mesons to final states with a b1 meson and a charged pion or kaon. The data, collected with the BABAR detector at the Stanford Linear Accelerator Center, represent 382x10(6) BB[over ] pairs produced in e+e- annihilation. The results for the branching fractions are, in units of 10(-6), B(B+-->b1(0)pi+)=6.7+/-1.7+/-1.0, B(B+-->b1(0)K+)=9.1+/-1.7+/-1.0, B(B0-->b1(-/+)pi(+/-))=10.9+/-1.2+/-0.9, and B(B0-->b1(-)K+)=7.4+/-1.0+/-1.0, with the assumption that B(b1-->omega pi)=1. We also measure charge and flavor asymmetries A(ch)(B+-->b1(0)pi+)=0.05+/-0.16+/-0.02, Ach(B+-->b1(0)K+)=-0.46+/-0.20+/-0.02, A(ch)(B0-->b1(-/+)pi(+/-))=-0.05+/-0.10+/-0.02, C(B0-->b1(-/+)pi(+/-))=-0.22+/-0.23+/-0.05, DeltaC(B0-->b1(-/+)pi(+/-))=-1.04+/-0.23+/-0.08, and A(ch)(B0-->b1(-)K+)=-0.07+/-0.12+/-0.02. The first error quoted is statistical, and the second systematic.     

Measurement of branching fractions and polarization in B-->phiK(*) decays

We present the first measurement of decay amplitudes in B-->phiK* and measurements of branching fractions in B-->phiK(*) decays based on 78.1 fb(-1) of data recorded at the Upsilon(4S) resonance with the Belle detector at the KEKB e+e- storage ring. The decay amplitudes for the different phiK*0 helicity states are measured from the angular distributions of final state particles in the transversity basis. The longitudinal and transverse complex amplitudes are |A0|2=0.43+/-0.09+/-0.04, |A(perpendicular)|2=0.41+/-0.10+/-0.04, arg((A(parallel))=-2.57+/-0.39+/-0.09, and arg((A(perpendicular))=0.48+/-0.32+/-0.06. The direct CP-violating asymmetries are found to be consistent with zero.     

Observation of B+ --> K0K+ and B0 --> K0K0

We report observations of the b --> d penguin-dominated decays B+ --> K0K+ and B0 --> K0K0 in 316 fb(-1) of e+ e- collision data collected with the BABAR detector. We measure the branching fractions B(B+ --> K0K+) = (1.61+/-0.44+/-0.09) x 10(-6) and B(B0 --> K0K0 = (1.08+/-0.28+/-0.11) x 10(-6) and the CP-violating charge asymmetry A(CP)(K0K+) = 0.10+/-0.26+/-0.03. Using a vertexing technique previously employed in several analyses of all-neutral final states containing kaons, we report the first measurement of time-dependent CP-violating asymmetries in B0 --> K(S)0K(S)0, obtaining S = -1.28(-0.73-0.16)(+0.80+0.11) and C = -0.40+/-0.41+/-0.06. We also report improved measurements of the branching fraction B(B+ --> K0 pi+) = (23.9+/-1.1+/-1.0) x 10(-6) and CP-violating charge asymmetry A(CP)(K0 pi+) = -0.029+/-0.039+/-0.010.     

Attenuation of ultrasound in suspensions of bovine muscle myofibrils and myosin

The attenuation of 1.5-7 MHz ultrasound was measured over the pH range 3-7 in 100 mM KCl suspensions of bovine M. semitendinosus myofibrils, precipitated myosin and the residue of myofibrils after partial extraction of myosin. In all fractions attenuation showed a similar dependence on pH over the range 3-7, with a broad, substantial maximum in the region of pH 4.5-pH 5.5 and similar mass attenuation coefficients (per g protein). At pH 7 and 7 MHz these were 3.49 +/- 0.20 cm2 g-1 in the myofibrils, 3.26 +/- 0.31 cm2 g-1 in the myofibrilar residue and 2.83 +/- 0.68 cm2 g-1 in the precipitated myosin. Measurements at 5.3 MHz of precipitated myosin over a wider pH range revealed an attenuation titration curve similar to that previously observed in homogenates of muscle and muscle myofibrils, with substantial peaks at about pH 5 and 11.5, and a shoulder perhaps indicating a small underlying peak at about pH 8-9. Myosin dissolved in 800 mM KCl gave attenuation levels that were typically 50% lower than precipitated myosin e.g. at pH 7 and 7 MHz: 2.83 +/- 0.68 cm2 g-1 in the precipitated form, 1.29 +/- 0.10 cm2 g-1 in solution. These results indicated that: (a) attenuation by myosin filaments contributed substantially to the total attenuation in suspensions of myofibrils and (b) the peak in the myofibrilar attenuation is caused, or substantially contributed to, by a process taking place in the myosin component.     

Metabolite mapping of human filarial parasite, Brugia malayi with nuclear magnetic resonance

Metabolite mapping of human filarial parasite, Brugia malayi was carried out in vitro as well as in situ in host Mastomys coucha by ³¹P nuclear magnetic resonance (NMR) spectroscopy. Detection of parasites by visualizing contrast spots due to pathologic changes was observed by ¹H magnetic resonance imaging (MRI). Major metabolites of adult B. malayi observed by ³¹P-NMR spectroscopy were of sugar phosphates (SP), phosphomonoesters (PME), glycerophosphoryl-ethanolamine (GPE), -choline (GPC), phosphoenolpyruvate (PEP), inorganic phosphate (Pi), nucleoside diphosphosugar and nucleotides-mono, -di and -tri phosphates. PEP and GPC were present in high concentration; PEP being the major energy reservoir and GPC the major phospholipid in this species of filaria. The ³¹P NMR spectra of testis of mastomys, showed seven major peaks of SP, PME, phosphocreatine (PCr), phosphodiesters (PDE), Pi, and nucleotides di- and tri-phosphates. The ³¹P-NMR spectra of testis of B. malayi infected animal also consisted of seven major peaks with significant decrease in the SP and PME peak showing changes in the carbohydrate and lipid metabolism of filaria infected testis. Thus, in vivo ³¹P MRS provided a non-invasive assessment of tissue bioenergetics and phospholipid metabolism.     

Storage effects on the quality quartet of orange juice submitted to moderate thermosonication: Predictive modeling and odor fingerprinting approach

The effects of moderate thermosonication (MTS) on the quality quartet: physico-chemical, microbial, nutritional and sensory qualities of orange juice (OJ) inoculated with Alicyclobacillus acidoterrestris (AAT) were studied during 24 days of storage at ambient and refrigerated temperatures. The bioactive compounds and antioxidant activity of OJ decreased with storage, while the pectin methyl esterase (PME) increased. Nonetheless, noticeable changes were observed from the 12th day of storage. There was no obvious (p > 0.05) variation in pH and total soluble solids. To determine the nutritional and microbial quality characteristics of OJ during storage, non-linear kinetic curves were successfully fitted with least square fitting polynomial and four-parameter log-logistic distribution models. The E-nose sensors succeeded in discriminating between the aroma of non-treated and treated OJ based on linear discriminant analysis (LDA). Furthermore, terpenes, alcohol and partially aromatic compounds were the main spoilage indicators of OJ during storage based on E-nose analysis and confirmed by HS-SPME-GC/MS analysis. Thus, MTS significantly extended the shelf life of the quality quartet of natural OJ at 4 °C. E-nose-GC/MS fusion offered odor fingerprints to AAT microorganisms that can be used as spoilage index without using traditional food analysis techniques. The proposed approach can be used as an alternative tool for rapid detection of spoilage microorganisms in OJ.     

Application of spectroscopic imaging in epilepsy

Functional and anatomical neuroimaging has had a dramatic effect on the evaluation of patients for seizure surgery. The demonstration by PET that the epileptogenic focus has interictal metabolic abnormalities has allowed a greater number of patients to come to seizure surgery, with fewer of these patients requiring intracranial electrode evaluations. Metabolic changes have also been demonstrated utilizing single voxel and whole brain ¹H and ³¹P MRS imaging techniques with the interictal focus characterized by increased Pi, pH, and decreased PME and NAA. These findings can be used to accurately lateralize temporal lobe as well as frontal lobe epilepsy. Furthermore, there is evidence that these findings can be used to localize the seizure focus with the changes specific for the epileptogenic region; although, more diffuse changes both ipsilaterally and contralaterally have been seen. In patients with anterior hippocampal seizure foci the pH is significantly alkaline only in the ipsilateral hippocampus, whereas the increased Pi and decreased PME can be seen throughout the ipsilateral temporal lobe. When compared to controls the contralateral hemisphere is acidotic. Decreased NAA concentrations as well as NAA/Cr ratios have been demonstrated in the epileptogenic region in temporal and frontal lobe epilepsy. The decreased NAA has been correlated with the severity of cell loss, and may be a more sensitive measure than qualitative or quantitative measures of the hippocampal atrophy; however, the NAA decrease is more widespread than just the epileptogenic focus but may be maximal at the site of seizure initiation. In preliminary work, NAA maps of deviation from normality have suggested the maximal change to coincide with the epileptogenic region. These results suggest that in focal epilepsy there is abnormal metabolic activity throughout the brain detectable by MRS, with patterns of metabolic asymmetry that are useful for seizure localization.     

Controlled ventilation during NMR spectroscopic studies: hemodynamic and biochemical consequences

The effects of different ventilation methods on cardiac output measured by the indicator-dilution method, liver blood flow measured by a deuterium washout technique using 2H nuclear magnetic resonance (NMR) and liver concentrations of ATP and intracellular pH determined with 31P NMR were compared in anesthetized rats. No differences in mean arterial blood pressure were demonstrable with the different modes of ventilation. However, significant drops in cardiac output were observed between freely breathing and animals ventilated with positive pressure but not the high frequency oscillatory method (407 +/- 46 and 520 +/- 88 vs. 633 +/- 86 ml/min/kg, p less than 0.05 and p = NS, respectively). Moreover, liver blood flow was significantly reduced during positive pressure but not high frequency oscillatory ventilation compared with free breathing rats (32 +/- 4 and 43 +/- 10 vs. 46 +/- 8 ml/100 g, p less than 0.05 and p = NS, respectively). 31P NMR spectroscopy revealed no effects of either ventilation method on tissue ATP or intracellular pH as estimated by the chemical shift of inorganic phosphate. These data suggest that controlled ventilation in normal rats accomplished with standard positive pressure methods is associated with major decreases in cardiac output and liver blood flow despite maintenance of normal blood pressure. High frequency oscillatory ventilation appears to effect less compromise of cardiac output and hepatic perfusion than positive pressure ventilation and may, therefore, be preferable for some biological studies.