Sleeve gastrectomy and Roux-en-Y gastric bypass exhibit differential effects on food preferences, nutrient absorption and energy expenditure in obese rats.

OBJECTIVE: All available treatments directed towards obesity and obesity-related complications are associated with suboptimal effectiveness/invasiveness ratios. Pharmacological, behavioral and lifestyle modification treatments are the least invasive, but also the least effective options, leading to modest weight loss that is difficult to maintain long-term. Gastrointestinal weight loss surgery (GIWLS) is the most effective, leading to >60-70% of excess body weight loss, but also the most invasive treatment available. Sleeve gastrectomy (SGx) and Roux-en-Y gastric bypass (RYGB) are the two most commonly performed GIWLS procedures. The fundamental anatomic difference between SGx and RYGB is that in the former procedure, only the anatomy of the stomach is altered, without surgical reconfiguration of the intestine. Therefore, comparing these two operations provides a unique opportunity to study the ways that different parts of the gastrointestinal (GI) tract contribute to the regulation of physiological processes, such as the regulation of body weight, food intake and metabolism. DESIGN: To explore the physiologic mechanisms of the two procedures, we used rodent models of SGx and RYGB to study the effects of these procedures on body weight, food intake and metabolic function. RESULTS: Both SGx and RYGB induced a significant weight loss that was sustained over the entire study period. SGx-induced weight loss was slightly lower compared with that observed after RYGB. SGx-induced weight loss primarily resulted from a substantial decrease in food intake and a small increase in locomotor activity. In contrast, rats that underwent RYGB exhibited a substantial increase in non-activity-related (resting) energy expenditure and a modest decrease in nutrient absorption. Additionally, while SGx-treated animals retained their preoperative food preferences, RYGB-treated rats experienced a significant alteration in their food preferences. CONCLUSIONS: These results indicate a fundamental difference in the mechanisms of weight loss between SGx and RYGB, suggesting that the manipulation of different parts of the GI tract may lead to different physiologic effects. Understanding the differences in the physiologic mechanisms of action of these effective treatment options could help us develop less invasive new treatments against obesity and obesity-related complications.

Visualization of nonstructural changes in early white matter development on diffusion-weighted MR images: evidence supporting premyelination anisotropy.

BACKGROUND AND PURPOSE: Previously, we showed that diffusion-weighted MR imaging depicts evidence of directionally preferential water motion in white matter structures of developing rat brain before and after myelination, and considerably earlier than conventional imaging strategies. Present data augment these imaging and corresponding histologic findings with electron-microscopic corroboration. We additionally report the findings of a 10-day-old rat pup tested functionally by administration of the sodium-channel blocker, tetrodotoxin. METHODS: In two rat pups, drawn from the population reported previously, MR estimates of diffusion anisotropy of the optic nerves and chiasm were compared with histologic and electron microscopy results. To test the hypothesis that "premyelination" directional preference of water motion in white matter structures relates to sodium-channel activity, MR imaging was performed in a 10-day-old rat pup treated with the sodium-channel blocker, tetrodotoxin, and findings were compared with data from an age-matched control. RESULTS: Although diffusion anisotropy was present in optic structures of the youngest animal, myelin-sensitive histologic staining did not show myelin before 12 days; electron microscopy confirmed lack of any myelin or its precursors during the earliest maturational stage. Administration of tetrodotoxin to the 10-day-old rat-pup led to loss of diffusion anisotropy. CONCLUSION: Our findings provide two pieces of supporting data for the hypothesis that nonstructural changes are responsible for early anisotropic diffusion: electron microscopy shows no evidence of myelin despite diffusion anisotropy, and inhibiting the sodium-channel pump appears to remove the directional preference of water motion. Visualization of nonstructural "premyelination" consequences with diffusion-weighted imaging emphasizes its sensitivity and potential in studying early processes of brain development.

Perfusion MR neuroimaging in patients undergoing balloon test occlusion of the internal carotid artery.

BACKGROUND AND PURPOSE: We sought to investigate whether the combination of conventional, diffusion-weighted, and perfusion-weighted MR imaging increases the diagnostic accuracy of balloon test occlusion of the internal carotid artery. We describe perfusion anomalies and patterns of enhancement seen in areas of altered brain perfusion during MR-monitored temporary balloon occlusion of the internal carotid artery. METHODS: Nine patients underwent balloon occlusion testing under standard angiographic conditions with continuous clinical and EEG monitoring. One patient who failed the test by clinical criteria underwent an external carotid to internal carotid bypass operation, followed by a repeat balloon test occlusion, thereby bringing the total number of procedures to 10. Patients were further imaged at 1.5 T with perfusion- and diffusion-weighted imaging as well as with conventional noncontrast and contrast-enhanced turbo fluid-attenuated inversion recovery (FLAIR) and T1-weighted sequences. RESULTS: Seven of 10 patients who tolerated unilateral carotid test occlusion without adverse clinical neurologic or EEG changes exhibited delayed first-pass transit of contrast material through the affected cerebral hemisphere, indicative of altered perfusion without significant concurrent cerebral blood flow or blood volume changes. Four of these patients and both symptomatic patients showed pial or subarachnoid contrast staining in areas of altered perfusion without abnormalities on diffusion-weighted images. CONCLUSION: Our findings indicate that MR perfusion-weighted imaging is safe and easily accomplished in a high-field-strength magnet and that contrast-enhanced turboFLAIR imaging may provide clinically useful MR imaging evidence of abnormal cerebral blood flow and subclinical ischemia.

Minimally invasive procedures. Interventional MR image-guided functional neurosurgery.

Intraoperative MR imaging techniques have the potential to greatly improve the stereotactic methods used for functional neurosurgery. No longer are neurosurgeons and patients always constrained by uncomfortable head frames and conventional stereotaxy. Accuracy and complication avoidance are improved by intraoperative imaging. Safety of operative machinery and equipment in an MR imaging operative suite is attainable, even with deep brain stimulating electrodes in depth electrodes for epilepsy. Although cost-effectiveness remains to be determined (see article by Kucharczyk et al in this issue), the minor inconveniences of operating within an iMRI environment seem to be significantly outweighed by the benefits.

Minimally invasive procedures. Advances in image-guided delivery of drug and cell therapies into the central nervous system.

Image-guided transparenchymal delivery of drugs is an emerging neurosurgical modality that holds the promise of delivering various agents directly across the blood-brain barrier. Potential large-scale applications for convection-enhanced delivery of drugs through the interstitial space include the delivery of chemotherapeutic agents and gene therapy vectors for the treatment of brain tumors and the delivery of neurotrophic factors and neurotransmitters for the treatment of neurodegenerative disorders. The related technique of direct intraparenchymal injection of cells provides a means for transplanting neural stem cells into the brain for the treatment of degenerative diseases. Significant advances in catheter design, infusion strategies, and imaging technology have brought these procedures into the mainstream of human clinical testing, with clinical applications potentially on the near horizon.

Cost-efficacy of MR-guided neurointerventions.

This article summarizes the available data on the cost-efficacy of interventional MR imaging and discusses its potential future role in the diagnosis and management of neurologic diseases and disorders.

Application of Salmonella strains with altered nitroreductase and O-acetyltransferase activities to the evaluation of the mutagenicity of airborne particles.

The Ames test was applied to evaluation of the mutagenicity of month's samples of airborne particles from the center of Wroclaw (SW Poland) collected in August and December 1997. The strains used for the study were TA 98, TA 100 and their derivatives: TA 98 NR, YG 1021, YG 1024, YG 1026, YG 1029, YG 1041, YG 1042. Both studied samples were mutagenic for almost all tested strains, with the exception of the August sample which did not influence the strain TA 100 without the metabolic activation with the S9 fraction. The December sample exhibited higher genotoxic activity than the August sample. Mutagenicity ratios of the strains with reduced nitroreductase and O-acetyltransferase activities were higher, and of the strain without the nitroreductase--lower than those of the parent strains. This indicates that nitro and amino derivatives of PAHs are responsible for the significant proportion of total mutagenicity of the studied samples of particulates. Metabolic activation with the S9 fraction caused the increase of the mutagenic activity of the samples, which indicates the presence of promutagens. The GC-MS analysis revealed the presence of known indirect mutagens from the PAHs group.

MRI compatibility and visibility assessment of implantable medical devices.

We have developed a protocol to evaluate the magnetic resonance (MR) compatibility of implantable medical devices. The testing protocol consists of the evaluation of magnetic field-induced movement, electric current, heating, image distortion, and device operation. In addition, current induction is evaluated with a finite element analysis simulation technique that models the effect of radiofrequency fields on each device. The protocol has been applied to several implantable infusion pumps and neurostimulators with associated attachments. Experiments were performed using a 1.5-T whole-body MR system with parameters selected to approximate the intended clinical and worst case configuration. The devices exhibited moderate magnetic field-induced deflection and torque but had significant image artifacts. No heating was detected for any of the devices. Pump operation was halted in the magnetic field, but resumed after removed. Exposure to the magnetic field activated some of the neurostimulators.

Diffusion-weighted MRI of myelination in the rat brain following treatment with gonadal hormones.

Previous studies have demonstrated the ability of high-resolution diffusion-weighted MRI to show maturation of white-matter structures in the developing rat brain. The purpose of this study was to investigate the influence of gonadal steroid hormones on the rate of this development. Starting from their second postnatal day, 16 rat-pups of either sex were repeatedly treated with subcutaneous implants containing 17-beta estradiol or delta-androstene 3,17 dione, respectively. Serial T1-, T2- and diffusion-weighted MRI was performed weekly for 8 weeks using a 4.7 T unit. Maturation of anterior optic pathways and hemisphere commissures was assessed. Diffusion-weighted images were processed to produce "anisotropy index maps", previously shown to be sensitive to white-matter maturation. Compared with untreated rat-pups, estrogen-treated animals showed accelerated, and testosterone-treated animals delayed maturation on anisotropy index maps and histological sections. In all animals, maturational changes appeared earlier on anisotropy index maps than on other MRI sequences or on myelin-sensitive stained sections. Diffusion-weighted imaging, and the construction of spatial maps sensitive to diffusion anisotropy, seem to be the most sensitive approach for the detection of maturational white-matter changes, and thus may hold potential for early diagnosis of temporary delay or permanent disturbances of white-matter development.

Sensitivity of high-speed "perfusion-sensitive" magnetic resonance imaging to mild cerebral ischemia.

This study assessed the sensitivity of contrast-enhanced dynamic echo-planar imaging to subtotal stenosis of the middle cerebral artery as a model of mildly compromised cerebral blood supply. Dynamic data was analyzed in terms of the relative cerebral blood volume (rCBV) and bolus peak arrival time (BPAT), and the prognostic utility of these parameters was compared with measurements of the regional apparent diffusion coefficient of water (ADC) with the goal of identifying tissue at risk of future infarct. Dynamic echo-planar MRI in conjunction with bolus administration of a magnetic susceptibility contrast agent was used in a cat model of acute, unilateral cerebral ischemia, induced by partial occlusion (stenosis) of the right middle cerebral artery. The contrast agent transit was analyzed in terms of the regional time of arrival of the peak bolus-induced signal loss as well as the time integral of agent concentration. Pixel-by-pixel maps of cerebrovascular parameters (rCBV, BPAT) were constructed along with spatial maps of the ADC, derived from diffusion-weighted MR images at the same anatomical level. Arterial stenosis was maintained for a 6 h period, after which histological determination of tissue viability was obtained. Maps of BPAT showed sensitivity to mild flow perturbations not detectable from cerebral blood volume estimations from the same bolus injection or from determinations of the apparent diffusion coefficient of water. Of nine animals subjected to subtotal stenosis, BPAT identified compromised tissue in all nine after 1 h of stenosis. No animals had differences in rCBV or ADC at this point. Stenosis was maintained for 6 h in 7 of the cats. After 6 h, two cats had developed identifiable injury on ADC and rCBV maps. Of the remaining five, where rCBV and ADC appeared normal even after 6 h, three exhibited abnormal histological staining, whereas two indeed appeared normal. In the other two cats where initial subtotal stenosis was later made total, the anatomical region identified as "compromised" during stenosis, by the appearance of delayed bolus peak arrival, matched the area of subsequent infarct after total occlusion of the same vessel. Echo planar imaging in conjunction with bolus administration of a magnetic susceptibility contrast agent appears sensitive to mild perturbations to blood supply. These perturbations may not be resolved on synthesized maps of relative cerebral blood volume or apparent diffusion coefficient. Although "compromised" blood supply does not necessarily lead to infarct (over the 6-h course of this study), it may represent tissue particularly at risk of infarct in the event of further insult.

Evaluation of recombinant human basic fibroblast growth factor (rhbFGF) as a cerebroprotective agent using high speed MR imaging.

The potential cerebroprotective effects of recombinant human basic fibroblast growth factor (rhbFGF) were evaluated in a feline model of acute cerebral ischemia using high-speed magnetic resonance imaging (MRI) in conjunction with immunohistology. The neuroprotective efficacy of three doses of rhbFGF was evaluated in a unilateral middle cerebral artery (MCA) occlusion/reperfusion model. Ten h following a 2 h period of MCA occlusion in control (vehicle-treated) animals, cerebral perfusion in the ischemic hemisphere was 58 +/- 17% of the contralateral normal hemisphere. Corresponding ischemic/normal perfusion ratios in rhbFGF-treated groups were not significantly different: 54 +/- 16% (14 micrograms/kg/h dose), 40 +/- 19% (42 micrograms/kg/h dose) and 75 +/- 8% (125 micrograms/kg/h dose). Triphenyltetrazolium chloride histopathological assessment demonstrated brain damage in vehicle-treated animals comprising 31 +/- 15% of the hemisphere; in rhbFGF-treated groups injury was not significantly different: 19 +/- 4% (14 micrograms/kg/h rhbFGF), 24 +/- 6% (42 micrograms/kg/h rhbFGF) and 16 +/- 10% (125 micrograms/kg/h rhbFGF). Immunohistochemical analysis of brain sections using glial fibrillary acidic protein (GFAP) revealed that in animals that showed marked perfusion deficits throughout the entire experiment (regardless of treatment), GFAP staining was elevated contralateral to the occlusion and absent ipsilaterally. While some tendency towards protection is found, particularly at higher doses of rhbFGF, it must be concluded that in the chosen stroke model and time interval, the doses used did not significantly improve reperfusion or confer significant cerebroprotective benefit. Non-invasive high-speed MRI was found to be useful for evaluation of putative cerebroprotective agents.

Age, gender, and vasopressin affect survival and brain adaptation in rats with metabolic encephalopathy.

Children and menstruant women are far more likely than men to develop metabolic brain damage from hyponatremia. We evaluated brain adaptation and mortality from hyponatremia in male and female rats of three different age groups. With acute hyponatremia, the mortality was 84% in prepubertal rats vs. 15% in adults and 0% in elderly rats. With chronic hyponatremia, mortality was 13% in adult males vs. 62% in females. Testosterone pretreatment significantly decreased mortality (from 62 to 9% in adult females, and from 100% to zero in prepubertal rats), but estrogen significantly increased mortality (from 13 to 44% in adult males). With acute hyponatremia in adult rats, brain sodium was significantly decreased (-17%), but in prepubertal rats it was actually increased (+ 37%). Cerebral perfusion during chronic hyponatremia was significantly impaired in adult females vs. males or controls (P < 0.01). Neither vasopressin administration nor chronic hyponatremia induced with desmopressin resulted in any mortality or decrement of cerebral perfusion. Thus age, gender, and the cerebral effects of vasopressin are major determinants of mortality in experimental metabolic encephalopathy.

Applications of magnetic source imaging to presurgical brain mapping.

This article highlights the patient benefits of noninvasive presurgical mapping using magnetic source imaging, discusses magnetic source imaging in terms of its practical implementation and current limitations in mapping the human cerebral cortex, and illustrates the use of magnetic source imaging in ongoing clinical studies. An overview of preliminary research studies that have attempted to evaluate the accuracy and cost-effectiveness of magnetic source imaging in presurgical mapping is also provided.

Hormonal dependence of the effects of metabolic encephalopathy on cerebral perfusion and oxygen utilization in the rat.

Previous studies have demonstrated that in adult rats with chronic hyponatremia, both symptoms of encephalopathy and mortality largely depend upon the gender of the animal and the presence of elevated plasma levels of vasopressin (AVP). Since effects of AVP on blood vessels may be gender dependent, the present study was designed to compare the effects of chronic (4 days) hyponatremia on cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and cerebral perfusion index (CPI) in adult male and female rats. CBF (intra-arterial 133Xe injection method) and CMRO2 (arteriovenous difference of cerebral oxygen contentxCBF) were measured in normonatremic and hyponatremic (hyponatremia induced with 140 mmol/L glucose and either AVP or desmopressin [dDAVP], plasma sodium = 100 to 110 mmol/L) adult rats of both genders. The CPI was assessed from magnetic resonance imaging of the transit of magnetic susceptibility contrast agent through the brain. Female rats with AVP-induced chronic hyponatremia had a 36% decrease in CBF and a 60% decrease in CMRO2. In male animals, both parameters were not different from control values. AVP-induced hyponatremia resulted in a 45% decrease in CPI in female rats, but hyponatremia induced with dDAVP did not affect CPI in either male or female rats. Chronic (4 days) administration of AVP did not affect CPI in either male or female normonatremic rats. When rats with AVP-induced chronic hyponatremia were pretreated with estrogen, the CPI in males was not different from that in females. Our results demonstrate that during AVP-induced chronic hyponatremia in female rats, there is significant depression of both oxygen utilization and blood flow in the brain.

NG-nitro-L-arginine delays the development of brain injury during focal ischemia in rats.

BACKGROUND AND PURPOSE: The present study was designed to determine the effect of nitro-L-arginine, the inhibitor of nitric oxide synthesis, on the evolution of cytotoxic brain edema during focal cerebral ischemia. METHOD: Diffusion-weighted and contrast-enhanced, perfusion-sensitive magnetic resonance imaging was performed in anesthetized, mechanically ventilated rats at 30 minutes and 1, 2, and 3 hours after occlusion of the middle cerebral artery combined with coagulation of the basilar artery. At the onset of ischemia, the animals were infused intravenously with 0.5 mL of either 0.9% NaCl or nitro-L-arginine (30 mg/kg). The severity of cytotoxic edema was evaluated based on changes in the water apparent diffusion coefficient (ADC) derived from diffusion-weighted images. The size of the area affected by ischemia was evaluated 3 hours after occlusion using 2,3,5-triphenyltetrazolium chloride (TTC) staining. RESULTS: The percentage decrease of ADC in the striatum of rats pretreated with nitro-L-arginine was significantly smaller (P < .05) than in the control group at 30 minutes and 1 and 2 hours of ischemia. The ADC in the injured cortex of nitro-L-arginine-treated rats did not differ significantly from the ADC value measured in the contralateral cortex until 3 hours after the occlusion. However, at 3 hours of ischemia the percentage decrease of ADC in both the striatum and the cortex of either group of rats was similar. This transient attenuation of ADC drop during ischemia after nitro-L-arginine pretreatment occurred concurrently with a transient improvement of blood supply to the ischemic regions. The percentage of hemispheric area with abnormal TTC staining after 3 hours of ischemia did not differ between control and nitro-L-arginine-treated rats. CONCLUSIONS: Nitro-L-arginine delays the development of ischemic injury by retarding cytotoxic brain edema. This effect is, at least partially, mediated by an improvement in blood supply to the ischemia tissues.

Identification of "premyelination" by diffusion-weighted MRI.

OBJECTIVE: The purpose of this study was to compare white matter maturation as demonstrated with diffusion-weighted MRI and with myelin-sensitive histological staining. MATERIALS AND METHODS: The diffusion-, T1-, and T2-weighted SE MRI at 4.7 T was performed weekly in a total of 16 rat pups, aged from 5 days to 8 weeks, 2 animals evaluated per week. Heavily diffusion-weighted sequences were obtained with the diffusion-sensitizing gradient switched alternately in two orthogonal directions. To enhance signal intensity of anisotropic structures, a synthesized image (referred to as the "anisotropy index map") was constructed from the ratio of pairs of images acquired with diffusion sensitization of identical magnitude but orthogonal direction sensitivity. The anisotropy index maps were used for comparison with T1-weighted and heavily T2-weighted SE sequences and histological sections, respectively. RESULTS: The first evidence of diffusion anisotropy on anisotropy index maps preceded initial myelin as well as neurofibril staining by 5-12 days and T2 shortening by 2 weeks. The T1-weighted sequences did not yield visible changes and were not helpful for the assessment of ongoing white matter maturation in this model. CONCLUSION: Magnetic resonance imaging signal intensity changes based on anisotropic water diffusion were demonstrated in regions of unmyelinated cerebral white matter tracts of albino rat pups before the onset of histologically detectable myelin. The ability of in vivo mapping of premyelinating white matter maturation indicates a new diagnostic use of MRI in evaluating cerebral white matter maturation.