Cho Ratios Research Articles

Botanical traits, protein and carbohydrate fractions, ruminal degradability and energy contents of alfalfa hay harvested at three stages of maturity and in the afternoon and morning

Little information is available about nutrient profiles and availability of alfalfa harvested at different stages of maturity and harvested at different times during the day in relation to diet formulation for dairy cows. The objective of this study was to investigate the effect of stage of maturity and cutting time of alfalfa hay on botanical traits, nutrient profiles and in situ degradability of protein and carbohydrates and calculated energy content. Alfalfa was cut at early bud (June 15/16), late bud (June 26/27) and early flower stage (July 18/19) both in the afternoon (06:00 pm) and the next morning (06:00 am). With advancing maturity of alfalfa, leaf content, leaf:stem ratio, calculated energy values, crude protein (CP), in situ digestibility's (especially at 12 and 36h of incubation) and nitrogen (N) to energy [organic matter (OM), carbohydrates (CHO)] ratios decreased (P<0.05). While, neutral detergent fiber, acid detergent fiber, fiber associated CP (NDICP) and total CHO increased (P<0.05) with advancing maturity of alfalfa. Protein and CHO fractions (defined according to Cornell net carbohydrate and protein system) associated with different degradation characteristics stayed consisted with advancing maturity, except for intermediate degradable protein (PB2), which decreased at the early flower stage compared with early and late bud stages (P=0.03). Alfalfa harvested in the afternoon tended to have a higher leaf portion and leaf:stem ratio (P=0.06) and contained 13g/kg CHO more soluble carbohydrates (TESC, i.e. CA; P<0.01), 27g/kg CP more PB2 (P=0.02), and 0.33, 0.33, 0.27MJ/kg DM more (P<0.05) net energy for maintenance, gain and lactation production, respectively, and had an improved rapidly degradable N to CHO ratio (PA:CA; 66 vs. 76g/kg; P=0.02) compared with alfalfa harvested in the morning. Cutting time had no impact on in situ degradability of alfalfa hay. In conclusion, nutrient availability of alfalfa hay, grown under semi arid climate condition, was not only influenced by stage of maturity but also by cutting time. In general, alfalfa harvested at early and late bud but in the afternoon had the highest nutrient levels for dairy production.

Benthic trophic status of sediments in a metropolitan area (Rio de la Plata estuary): Linkages with natural and human pressures

We evaluated the benthic trophic status of the Montevideo coastal zone-Rio de la Plata estuary using the quantity and the biochemical composition of sedimentary organic matter as synthetic descriptors. The spatio-temporal patterns in the biochemical composition of sedimentary organic matter were related to the presence of some natural and human pressures. Biochemical features were analyzed correlatively with the type and proximity of certain impacts to investigate the usefulness of this biochemical approach for assessing the levels of natural and anthropogenic perturbations. Chlorophyll-a, phaeopigment and the biopolymeric carbon concentrations were similar to those reported in very productive, eutrophic and anthropised estuarine areas. Total proteins (PRT) and lipids (LIP) showed the highest concentrations in the inner portion of Montevideo Bay, decreasing towards the nearby coastal areas of Punta Carretas and Punta Yeguas. Total carbohydrates (CHO) presented the lowest values in the outer stations of Montevideo Bay, but similar and higher concentrations were recorded in the inner stations of the bay and the adjacent coastal zones. PRT:CHO ratios >1 were always observed for the inner stations of Montevideo Bay thus suggesting intense detritus mineralization and an increment in their protein content due to bacterial activity. The biopolymeric carbon showed the same spatial trend observed for PRT, LPD and the PRT: CHO ratios with highest concentrations in the inner bay than in Pta. Carretas and Pta. Yeguas. Elevated contributions of PRT and LIP in the inner Montevideo Bay may be associated with anthropogenic inputs of organic matter such as sewage, food industry and petroleum hydrocarbons. Conversely, high CHO contributions in the nearby coastal areas of Pta. Carretas and Pta. Yeguas seemed to be related to autochthonous primary production and CHO temporal variability with natural oscillations in the productivity of the system. Biochemical composition of organic matter indicates hypertrophic conditions and poor environmental quality in the sediments of the inner stations of Montevideo Bay due to strongest human impact. However, biochemical descriptors showed a relative improvement of the benthic trophic status in the external coastal areas subjected to moderate levels of anthropogenic pressure. This study confirmed the utility of this biochemical approach to establish zones with distinct benthic trophic status associated to different degrees of natural and human pressures. Nevertheless, our results suggest that threshold levels for PRT, BPC and the algal contribution to the BPC that properly reflect hypertrophic conditions should be further investigated.

A randomized controlled clinical trial of growth hormone in amyotrophic lateral sclerosis: clinical, neuroimaging, and hormonal results

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease with motor neuron degeneration. Riluzole is the only available treatment. Two-thirds of ALS patients present with growth hormone (GH) deficiency. The aim of this study is to determine if add-on of GH to riluzole, with an individually regulated dose based on Insulin-like growth factor 1 (IGF-I) production, was able to reduce neuronal loss in the motor cortex, reduce mortality, and improve motor function of ALS patients. Patients with definite/probable ALS, in treatment with riluzole, aged 40-85 years, and with disease duration ≤3 years were enrolled. The study was randomized, placebo controlled, and double blind. Before treatment, patients were tested with a GH releasing hormone (GHRH) + arginine test. The initial dose of GH was 2 IU s.c. every other day, and was progressively increased to a maximum of 8 IU. Primary endpoint was N-acetylaspartate/(creatine + choline) (NAA/Cre + Cho) ratio in motor cortex assessed by magnetic resonance spectroscopy performed at months 0, 6, and 12. Secondary endpoints were mortality and ALS functional rating scale revised (ALSFRS-R). The NAA/(Cre + Cho) ratio decreased in all patients who completed the trial. No significant difference was noted between treated and placebo group. At baseline, although IGF-I levels were within the normal range, 73% of patients had GH deficiency, being severe in half of them. Compared with bulbar onset, spinal-onset patients showed more depressed GH response to the GHRH + arginine stimulation test (10.4 ± 7.0 versus 15.5 ± 8.1 ng/mL; p < 0.05). Insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] increased from 2.1 ± 1.0 at baseline to 4.6 ± 1.9 at 12 months (p < 0.001). Insulin-like growth factor (IGF) binding protein 3 (IGFBP-3) decreased from 8,435 ± 4,477 ng/mL at baseline to 3,250 ± 1,780 ng/mL at 12 months (p < 0.001). The results show that GH exerted no effect on cerebral NAA or clinical progression assessed by ALSFRS-R. Two-thirds of ALS patients had GH deficit, with higher levels in the bulbar-onset group. During follow-up, patients showed progressive increase in HOMA-IR and decrease in IGFBP-3 levels.

Brain metabolism in fetal intrauterine growth restriction: a proton magnetic resonance spectroscopy study

The purpose of this study was to investigate alterations in brain metabolism in fetuses with intrauterine growth restriction (IUGR) and evidence of cerebral redistribution of blood flow. Biometry and Doppler assessment of blood flow was assessed with ultrasound in 28 fetuses with IUGR and cerebral redistribution and in 41 appropriately grown control subjects. Proton magnetic resonance spectroscopy of the fetal brain was then performed to determine the presence of choline (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate and to generate ratios for NAA:Cho, NAA:Cr, and Cho:Cr. Sixty-five percent of spectra were interpretable: N-acetylaspartate, choline, and creatine peaks were identified in all these spectra; lactate was present in 5 IUGR fetuses and in 3 appropriately grown fetuses. NAA:Cr and NAA:Cho ratios were significantly lower in IUGR fetuses with cerebral redistribution. Cerebral redistribution is associated with altered brain metabolism that is evidenced by a reduction in NAA:Cho and NAA:Cr ratios.

Temporal evolution of sporadic Creutzfeldt–Jakob disease monitored by 3-Tesla MR spectroscopy

Creutzfeldt–Jakob disease (CJD) is a progressive neurodegenerative disease. How the lesions of CJD initiate and propagate in the brain remains largely unknown. Magnetic resonance (MR) techniques including proton MR spectroscopy (MRS) are useful for diagnosing CJD [1–3]. MRS allows for noninvasive and spatially resolved measurement of several brain compounds, including N-acetyl aspartate (NAA), a neuronal marker, and choline-containing compounds (Cho), a marker of membrane density and integrity [4]. However, the use of MRS to investigate the temporal evolution of CJD has been limited. We analyzed serial 3-Tesla MRS findings in patients with sporadic CJD (sCJD). Two patients with diagnoses of probable (case 1) and definite (case 2) sCJD [5] were enrolled. The profiles of patients are summarized in Table 1. MRS examinations were performed using a 3-Tesla MR unit (Signa 3T HDx; GE Medical Systems, Milwaukee, WI, USA). Each patient underwent the sessions twice at intervals of 4 (case 1) and 6 (case 2) weeks. MR spectra were obtained using the multivoxel method performed with chemical shift imaging (repetition time/echo time = 1,500/144 ms). The MRS values from voxels of interest in the left cerebrum were analyzed (Fig. 1a). The comparison was made between the two MRS studies in each patient. The values of NAA, Cho, lactate, and the Cho to NAA ratio (Cho/NAA) were compared using Student’s t tests. Statistical significance was accepted for p \ 0.05. This study was approved by the Ethics Committee and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. In case 1, the MRS analysis showed a significant decrease in NAA (p \ 0.05, Fig. 1b), a trend toward increased Cho (mean values, 1,100 vs. 1,314, p = 0.07), and a significant increase in the Cho/NAA (p \ 0.005, Fig. 1c) over time. In case 2, although a decrease in NAA was found, it was not significant (mean values, 238 vs. 163, p = 0.29), there were no significant temporal changes in Cho (mean values, 428 vs. 470, p = 0.78), and the Cho/ NAA was significantly increased (p \ 0.005, Fig. 1d). Interestingly, lactate peaks were noted in all sessions of both cases. The lactate values were not significantly different in the serial studies of each case (mean values: case 1, 146 vs. 163, p = 0.52; case 2, 105 vs. 145, p = 0.25). In case 2, a necropsy of the left frontotemporal lobe confirmed the diagnosis of definite sCJD (Fig. 1e–f). Our study revealed that the Cho/NAA increased over time and lactate peaks were present in the 3-Tesla MRS studies of patients with sCJD. A reduced NAA to Cho ratio (or elevated Cho/NAA) has been reported in familial CJD [6]. Increases in Cho/NAA have also been reported in malignant tumors, cerebral infarctions, inflammation, and K. Fujita (&) Y. Izumi R. Kaji Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan e-mail: kof@clin.med.tokushima-u.ac.jp

MR spectroscopy of normative premature newborns

To establish normative metabolite ratios throughout the newborn brain using three-dimensional (3D) MR spectroscopic imaging (MRSI). MRI and MRSI have been valuable tools for assessing normal and abnormal neuronal maturation for newborns. In this study, we performed whole brain 3D MRSI in addition to comprehensive anatomic and other functional imaging methods to examine maturation. Fifty-five newborn subjects (28.4 ± 2.6 weeks postconception age at birth, 34.1 ± 3.1 weeks postconception age at scan, 32 males and 23 females) had high quality MRSI studies (104 exams) and normal neurodevelopmental outcome (neuromotor score = 0, mental development index score > 85) at age 12 months. The NAA to Cho ratio increased significantly with age for all regions. Lac to NAA ratio decreased significantly with age in the regions of thalamus, basal ganglia, cortical spinal tract, and parietal white matter, and showed a decreasing trend in the other regions. Brain metabolites can be obtained through in vivo 3D MRSI and used to monitor newborn brain maturation.

The Fat:Carbohydrate Energy Ratio of the Weaning Diet Programs Later Susceptibility to Obesity in Male Sprague Dawley Rats 3

Dietary fat intake, which is high during suckling, is markedly reduced when food and drinks are introduced into the diet. We investigated whether alterations in the fat:carbohydrate (CHO) content of the weaning diet influenced the later development of adiposity and insulin sensitivity. Three groups of male rats (24/group) were fed from age 16–37 d (phase I) with weaning diets varying in their fat:CHO energy (E) ratios, 10:70 low-fat, high-CHO (LFHC); 30:50 medium-fat, medium-CHO (MFMC), and 60:30 high-fat, high-CHO (HFLC), on an isocaloric basis. Then, all groups consumed ad libitum first a low-fat diet (13% fat E) for 30 wk (phase II) and subsequently a high-fat diet (45% fat E) for another 18 wk (phase III). At the end of phase I, the group fed the HFLC diet demonstrated higher plasma glucose and insulin responses to an oral glucose tolerance test (P < 0.05), but this effect was transient and did not persist into adulthood (phases II and III). By contrast, when challenged with a high-fat diet later in life (age 35.3–53.3 wk), the LFHC group had greater gains in weight (as percent initial weight) and body fat (as absolute and percent body weight) than the other 2 groups that had been weaned with diets higher in fat (P < 0.04 for all). These results provide evidence that metabolic programming by altering the dietary fat:CHO ratio can occur during the weaning period and emphasizes the importance of the fat:CHO ratio of the complementary diet and its relation to the susceptibility to develop adiposity later in life.

Nutrient composition and degradation profiles of anthocyanidin-accumulating Lc-alfalfa populations

Alfalfa (Medicago sativa L.) is one of the most used forages in the world but suffers the disadvantage of having poor protein utilization by the animal. The poor protein utilization is the result of excessive ruminal protein degradation, which might be reduced by the protein precipitating capacity of anthocyanidin (AC) and condensed tannins (CT). The objective of this study was to determine the effects of the Lc-transgene on survival, anthocyanidin, condensed tannin and chemical profiles in crossed populations of western Canadian-adapted Lc-alfalfa. These were compared with their non-transgenic (NT) parental varieties, Rangelander, Rambler, and Beaver. Lc-alfalfa forage accumulated enhanced amounts of anthocyanidin, with an average concentration of 197.4 µg g-1 DM, while condensed tannins were not detected. Both of these metabolites were absent in the NT parental varieties. Lc-alfalfa had a lower (24.8 vs. 27.3% DM; P &lt; 0.02) crude protein (CP) and higher (58.3 vs. 55.5% DM; P &lt; 0.01) carbohydrate (CHO) concentration, which resulted in their decreased (P &lt; 0.01) N:CHO ratio (68.1 vs. 79.2 g kg-1) compared with NT alfalfa. Slowly degradable N:CHO ratio was decreased by 5.9 g kg-1 (P &lt; 0.03) and total rumen-degradable N:CHO ratio was decreased by 12.9 g kg-1 (P &lt; 0.03) in Lc-alfalfa compared with NT alfalfa. In conclusion, Lc-gene transformation resulted in the accumulation of anthocyanidin, decreased total protein content, increased total carbohydrate content and improved the balance between nitrogen and carbohydrates in the crossed transgenic populations of western Canadian-adapted alfalfa compared to their NT western Canadian parental alfalfa varieties. Key words: Alfalfa, anthocyanidin, Lc-transgene, protein and carbohydrate sub-fractions, nitrogen-to-carbohydrate degradation ratios

1H-MR Spectroscopy Changes in Transient Ischemic Attack Patients and Their Correlation with Perfusion-Weighted Imaging

ABSTRACTPurpose: We investigated whether patients with transient ischemic attack (TIA) have metabolic changes in the brain. Methods: 35 patients with clinically diagnosed TIA were prospectively included in our study. Clinical and neurological data were compiled. 1H-MR spectroscopy and perfusion-weighted imaging were performed in all patients within 3 days of the onset of symptoms. Results: In TIA patients, the N-acetylaspartate (NAA)/choline (Cho) ratio in noninfarcted regions was significantly decreased in the symptomatic hemisphere (1.33 ± 0.38) compared with the asymptomatic hemisphere (1.51 ± 0.41, p < .05). Patients with a history of prior TIA had a significantly decreased NAA/Cho ratio in both the symptomatic (p < .05) and asymptomatic (p < .05) hemispheres compared with TIA patients without a prior TIA. TIA patients with diffusion-weighted imaging lesions had a significantly increased lactate/NAA ratio in both the symptomatic (p < .05) and asymptomatic (p < .05) hemispheres compared with TIA patients without lesions. The relative cerebral blood flow (rCBF) value was directly related to the symptomatic Cho/creatine (Cr) value (r = 0.81, p < .01). The higher the rCBF value, the higher the symptomatic Cho/Cr value. Conclusions: TIA patients have neurological deficits that are transient; however, metabolic damage to the brain is present up to 3 days after the onset of the symptoms. These metabolic changes are not restricted to the symptomatic hemisphere or to areas close to ischemic lesions and the changes are related in the CBF.

Monitoring of treatment response after chemoradiotherapy for head and neck cancer using in vivo 1H MR spectroscopy

Elevated choline (Cho) level has been documented on proton magnetic resonance spectroscopy ((1)H MRS) in head and neck squamous cell carcinoma and therefore percentage changes in Cho levels after chemoradiotherapy may serve as a marker of residual cancer in a post-treatment mass (PTM). Forty-six patients underwent (1)H MRS before treatment and the 30 patients with a PTM underwent repeat (1)H MRS at 6 weeks post-treatment. The percentage change in Cho/creatine and Cho/water ratios were correlated with residual cancer. The mean pretreatment Cho/creatine and Cho/water ratios were 2.24 and 1.20 x 10(-3), respectively. Cho persisted in four out of nine PTMs with residual cancer. Cho was absent in five out of nine PTMs with residual cancer and 21/21 PTMs without cancer. The number of PTMs with persistent Cho was too small to allow analysis of percentage change in ratios but the presence of Cho in a PTM showed significant correlation with residual cancer (p = 0.0046), producing a sensitivity, specificity, positive predictive value and negative predictive value of 44%, 100%, 100% and 81%, respectively. Therefore, the presence of Cho in a PTM may serve as a marker of residual cancer. Furthermore since so few PTMs contain Cho, a percentage change in Cho ratios may not be a useful method for monitoring treatment response.

Clinical Update on Optimal Prandial Insulin Dosing Using a Refined Run-to-Run Control Algorithm

This article provides a clinical update using a novel run-to-run algorithm to optimize prandial insulin dosing based on sparse glucose measurements from the previous day's meals. The objective was to use a refined run-to-run algorithm to calculate prandial insulin-to-carbohydrate ratios (I:CHO) for meals of variable carbohydrate content in subjects with type 1 diabetes (T1DM). The open-labeled, nonrandomized study took place over a 6-week period in a nonprofit research center. Nine subjects with T1DM using continuous subcutaneous insulin infusion participated. Basal insulin rates were optimized using continuous glucose monitoring, with a target fasting blood glucose of 90 mg/dl. Subjects monitored blood glucose concentration at the beginning of the meal and at 60 and 120 minutes after the start of the meal. They were instructed to start meals with blood glucose levels between 70 and 130 mg/dl. Subjects were contacted daily to collect data for the previous 24-hour period and to give them the physician-approved, algorithm-derived I:CHO ratios for the next 24 hours. Subjects calculated the amount of the insulin bolus for each meal based on the corresponding I:CHO and their estimate of the meal's carbohydrate content. One- and 2-hour postprandial glucose concentrations served as the main outcome measures. The mean 1-hour postprandial blood glucose level was 104 +/- 19 mg/dl. The 2-hour postprandial levels (96.5 +/- 18 mg/dl) approached the preprandial levels (90.1 +/- 13 mg/dl). Run-to-run algorithms are able to improve postprandial blood glucose levels in subjects with T1DM.

Children and adolescents on intensive insulin therapy maintain postprandial glycaemic control without precise carbohydrate counting

Carbohydrate (CHO) quantification is used to adjust pre-meal insulin in intensive insulin regimens. However, the precision in CHO quantification required to maintain postprandial glycaemic control is unknown. We determined the effect of a +/-10-g variation in CHO amount, with an individually calculated insulin dose for 60 g CHO, on postprandial glycaemic control. Thirty-one children and adolescents (age range 9.5-16.8 years), 17 using continuous subcutaneous insulin infusion (CSII) and 14 using multiple daily injections (MDI), participated. Each subject consumed test lunches of equal macronutrient content, differing only in carbohydrate quantity (50, 60, 70 g CHO), in random order on three consecutive days. For each participant, the insulin dose was the same for each meal, based on their usual insulin : CHO ratio for 60 g CHO. Activity was standardized. Continuous glucose monitoring was used. The CSII and MDI subjects demonstrated no difference in postprandial blood glucose levels (BGLs) for comparable carbohydrate loads (P > 0.05). The 10-g variations in CHO quantity resulted in no differences in BGLs or area under the glucose curves for 2.5 h (P > 0.05). Hypoglycaemic episodes were not significantly different (P = 0.32). The 70-g meal produced higher glucose excursions after 2.5 h, with a maximum difference of 1.9 mmol/l at 3 h (P = 0.01), but the BGLs remained within international postprandial targets. In patients using intensive insulin therapy, an individually calculated insulin dose for 60 g of carbohydrate maintains postprandial BGLs for meals containing between 50 and 70 g of carbohydrate. A single mealtime insulin dose will cover a range in carbohydrate amounts without deterioration in postprandial control.

Proton magnetic resonance spectroscopy of the frontal, cingulate and perirolandic cortices and its relationship to skin conductance in patients with schizophrenia

The aim of the present study was to determine whether specific subgroups of schizophrenic patients, grouped according to electrodermal characteristics, show differences in the N-acetylaspartate/creatine plus choline (NAA / (Cr + Cho)) ratios in the frontal, cingulate and perirolandic cortices. Skin conductance levels (SCL) and skin conductance responses to auditory stimulation were measured in 38 patients with schizophrenia and in the same number of matched healthy volunteers (control). All subjects were submitted to multivoxel proton magnetic resonance spectroscopic imaging. When compared to the control group, patients presented significantly lower NAA / (Cr + Cho) ratios in the right dorsolateral prefrontal cortex (schizophrenia = 0.95 +/- 0.03; control = 1.12 +/- 0.04) and in the right (schizophrenia = 0.88 +/- 0.02; control = 0.94 +/- 0.03) and left (schizophrenia = 0.84 +/- 0.03; control = 0.94 +/- 0.03) cingulates. These ratios did not differ between electrodermally responsive and non-responsive patients. When patients were divided into two groups: lower SCL (less than the mean SCL of the control group minus two standard deviations) and normal SCL (similar to the control group), the subgroup with a lower level of SCL showed a lower NAA / (Cr + Cho) ratio in the left cingulate (0.78 +/- 0.05) than the controls (0.95 +/- 0.02, P < 0.05) and the subgroup with normal SCL (0.88 +/- 0.03, P < 0.05). There was a negative correlation between the NAA / (Cr + Cho) ratio in the left cingulate of patients with schizophrenia and the duration of the disease and years under medication. These data suggest the existence of a schizophrenic subgroup characterized by low SCL that could be a consequence of the lower neuronal viability observed in the left cingulate of these patients.

N-Acetylaspartate/Creatine and Choline/Creatine Ratios in the Thalami, Insular Cortex and White Matter as Markers of Hypertension and Cognitive Impairment in the Elderly

Our objective was to investigate the influence of hypertension on N-acetylaspartate (NAA) and choline (Cho) ratios in brain tissues in a community-dwelling elderly population. Brain flexibility was also evaluated with regard to the same metabolite ratios. Proton magnetic resonance spectroscopy (MRS) and the Trail Making Test (TMT) were performed in 80 subjects (75.7+/-4 years old) from the Three-City Study. Fifty-eight participants had hypertension. The NAA/creatine (Cr) and Cho/Cr ratios were obtained in the insular cortex, the thalami and the deep periventricular white matter. In addition, the B-A score of the TMT was evaluated. Uni- and multi-variate analyses were performed in order to examine the relationships among these data. In the insula and the thalami of the hypertensive group, NAA/Cr ratios were significantly lower (1.39+/-0.23 and 1.52+/-0.23, respectively; p=0.01) than those in the normotensive control group (1.52+/-0.25 and 1.70+/-0.19, respectively; p<0.0001), whereas no such reduction was observed in the periventricular white matter of older hypertensive brains. Moreover, the NAA or Cho ratios were significantly correlated with the TMT B-A scores at the level of the thalami, insula and periventricular white matter. These statistical results were confirmed by the multivariate analysis. In an elderly population, hypertension leads to a reduction in NAA/Cr ratios in the insula and the thalami, possibly due to a decrease in blood flow through small perforating and cortical arteries. The TMT B-A test appears to be relevant not only for the frontal areas but also for more remote areas such as the thalami, the insula and the deep periventricular white matter.

Serial 1H-MRS of thalamus during deep brain stimulation of bilateral globus pallidus internus for primary generalized dystonia

The physiological mechanisms of deep brain stimulation (DBS) are not completely clear. Our understanding of them may be facilitated with the use of proton magnetic resonance spectroscopy ((1)H-MRS). Serial (1)H-MRS of both thalami was performed during the course of DBS of bilateral globus pallidus internus in a patient with primary generalized dystonia. Two days after microelectrode implantation, a pulse frequency of 185 Hz was applied for stimulation. It resulted in relief of symptoms and a decrease of Burke-Fahn-Marsden dystonia rating scale (BFMDRS) scores, and was accompanied by a prominent increase of N-acetylaspartate (NAA)/choline-containing compounds (Cho) ratio, a mild increase of NAA/creatine (Cr) ratio, and a moderate decrease of Cho/Cr ratio. Two weeks later, for a search of the optimal stimulation mode, the pulse frequency was switched to 60 Hz, which resulted in clinical deterioration and significant increase of BFMDRS scores. At that time, all investigated (1)H-MRS-detected metabolic parameters had nearly returned to the pretreatment levels. Use of serial (1)H-MRS investigations of various brain structures during DBS in cases of movement disorders permits detailed evaluation of the treatment response, has a potential for its possible prediction, and may facilitate understanding of the physiological mechanisms of stimulation.

Impact of the Brain-Derived Neurotrophic Factor Val66Met Polymorphism on Levels of Hippocampal N-Acetyl-Aspartate Assessed by Magnetic Resonance Spectroscopic Imaging at 3 Tesla

This study was conducted to corroborate prior evidence of an effect of the brain-derived neurotrophic factor (BDNF) valine (val) to methionine (met) amino acid substitution at codon 66 (val66met) polymorphism on measures of N-acetyl-aspartate (NAA) containing compounds in healthy subjects. The NAA to creatine (Cre) ratio (NAA/Cre), NAA to choline (Cho) ratio (NAA/Cho), and Cho to Cre ratio (Cho/Cre) were measured in the left and right hippocampi, left and right dorsolateral prefrontal cortices, occipital lobe, anterior cingulate, and white matter of the centrum semiovale of 69 carefully screened healthy volunteers utilizing proton magnetic resonance spectroscopic imaging (MRSI) at 3 Tesla (T). Val/met subjects exhibited significantly reduced levels of left hippocampal NAA/Cre and NAA/Cho compared with val/val subjects. This effect was independent of age, IQ, number of voxels, hippocampal volume, or gray matter content in the voxels of interest. Analysis of other brain regions showed no effect of BDNF genotype on NAA measures. We confirmed the association between the met-BDNF variant and reduced levels of hippocampal NAA found with a similar technique at 1.5T. The consonance of our results with prior findings adds to the evidence that the BDNF val/met genotype affects hippocampal biology with implications for a variety of neuropsychiatric disorders.

Multivoxel MR Spectroscopic Imaging – Distinguishing Intracranial Tumours from Non-neoplastic Disease

Multi-voxel MR spectroscopic imaging (MRSI) provides chemical metabolite information that can supplement conventional MR imaging in the study of intracranial neoplasia. Our purpose was to use a robust semi-automated spectroscopic analysis to distinguish intracranial tumours from non-neoplastic disease. Twenty intracranial tumours and 15 patients with non-neoplastic disease confirmed on histological examination or serial neuroimaging were studied with 2-dimensional MRSI using point-resolved spectroscopic (PRESS) imaging localisation. Using semi-automated post-processing software, spectra were analysed for peak heights of choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), lactate (Lac) and lipid (Lip). Normalised Cho (nCho) ratios, computed by dividing maximum Cho in the lesion by the normal-appearing brain, were compared between intracranial tumours and non-neoplastic disease. Meningiomas displayed homogeneously elevated Cho. Malignant tumours, especially large glioblastoma multiforme, displayed inhomogeneity of metabolites within the tumour. All tumours had elevation of nCho >1 (mean 1.91 +/- 0.65), and non-neoplastic diseases had tumour nCho <1 (mean 0.91 +/- 0.46), which was significantly lower (P <0.05). Two patients with non-neoplastic lesions, one with subacute cerebral infarction and the other with cryptococcoma, had elevated Cho compared to normal tissue (false positive rate 13%). Using semi-automated MRSI method, a simplified normalised Cho algorithm provides a method to distinguish intracranial tumours from non-neoplastic disease.

Use of glycemic load to monitor carbohydrates in patients on ketogenic therapy

Ketogenic therapy (KT) has historically been used to treat patients with intractable epilepsy. It consists of high fat, adequate protein, and minimum carbohydrate (CHO) with the emphasis on the fat to protein plus CHO ratio. The glycemic load (GL) is a value calculated from the amount of CHO consumed and the effect of the CHO on plasma glucose. Foods with simple CHO have higher GLs and foods with complex CHO have lower GLs. Traditionally, the type of carbohydrates being given to KT patients is not monitored. This study's purpose was to determine if this monitoring would be valuable. Diet recalls from 15 pediatric patients on KT were obtained and analyzed by the University of Minnesota's Nutrition Data System (NDS). The total GLs (with both glucose and white bread as references), total CHO, CHO/kg/day, and GL/kg/day were determined. Linear regressions were done for total CHO vs. GL and for CHO/kg/day for GL/kg/day. Total CHO vs. GL had an r2 of 0.7971 and p‐value 0.0004 and CHO/kg/day vs. GL/kg/day had an r2of 0.8283 and a p‐value of 0.0001. As expected, linear regressions reveal significant correlation between CHO and GL and CHO/kg/day and GL/kg/day, but do not account entirely for all the data. For example, one patient received 34.4 g CHO per day and had a GL of 16.7 whereas another patient who received 21.5 g CHO per day had a higher GL of 21.1. These data indicate monitoring the types of carbohydrates given to patients on KT may be beneficial.

Magnetic resonance spectroscopy of the thalamus in patients with mesial temporal lobe epilepsy and hippocampal sclerosis.

to investigate potential neuronal dysfunction within the thalamus in patients suffering from mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE/HS). we examined twenty epileptic patients suffering from mesial temporal lobe epilepsy with hippocampal sclerosis (17 females, 3 males) and twenty sex- and age-matched healthy controls. H MR spectroscopic imaging (SI) was performed over the right and left thalamus in all patients and controls. In addition both hippocampi were investigated by the H MR spectroscopic single voxel (SV) technique in both groups. statistical analysis of compared data in both groups demonstrated that the total thalamic NAA level was significantly decreased in patients with MTLE/HS as compared to healthy controls. Detailed analysis revealed a statistically significant reduction of NAA, NAA/Cr and NAA/(Cr+Cho) ratios in the thalamus ipsilateral to hippocampus affected with hippocampal sclerosis in patients compared to controls, while no significant changes were observed in the thalamus contralateral to sclerotic hippocampus. A comparison of values in ipsilateral and contralateral thalami in patients showed statistically significant difference with lower values of NAA and both ratios in the ipsilateral thalamus. Previously reported reduced hippocampal concentration of NAA, NAA/Cr and NAA/(Cr+Cho) ratios on the side of hippocampal sclerosis compared with contralateral hippocampus in patients and both hippocampi in controls was confirmed. the present MRS data clearly indicate neuronal dysfunction within the thalamus ipsilateral to the sclerotic hippocampus of patients with mesial temporal lobe epilepsy. In agreement with other recent functional and structural neuroimagings our results confirm the role of the ipsilateral thalamus in the medial temporal/limbic epileptic network.

MRI and 1H-MRS detects volumetric and metabolic abnormalities of hippocampal sclerosis in temporal lobe epilepsy

Objective To further investigate the ability of MRI and 1H-MRS techniques for presurgical evaluation of hippocampal sclerosis. Methods MRI and 1H-MRS were performed on 30 healthy subjects to determine the confidence levels. Eight patients who were pathologically confirmed hippocampal sclerosis were then studied using the same protocols. The difference of hippocampal formation (DHF) was used to determine atrophy of hippocampus. Areas under the peak of N-acetylaspartate(NAA), Creatine(Cr) and Choline (Cho) were measured, and the ratios of NAA/Cr, Cho/Cr, and NAA/Cr+Cho were calculated. NAA/Cr+Cho value was applied to localize the seizure focus. Results Two patients showed hippocampal atrophy according to DHF value. NAA/Cr ratio decreased significantly in ipsilateral hippocampus compared to that in contralateral hippocampus and control subjects( P < 0.01). Cho/Cr value increased in both ipsi- and contralateral hippocampus in comparison with that in control subjects( P < 0.01). NAA/Cr+Cho ratio, however, significantly reduced in both ipsi-and contralateral hippocampus( P < 0.01) with lowest NAA/Cr+Cho ratio in seizure foci. Six patients could be lateralized by reduced and/or asymmetric NAA/Cr+Cho value. Conclusion 1H-MRS should be a promising diagnostic tool to detect neuron abnormality. 1H-MRS and MRI complement each other in presurgical lateralization of epileptogenic lesion in epilepsy patients.