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.

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.

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.

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.

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.

Diffusion-weighted magnetic resonance imaging of acute focal cerebral ischemia: comparison of signal intensity with changes in brain water and Na+,K(+)-ATPase activity.

Diffusion-weighted magnetic resonance (MR) images from rats during acute cerebral ischemia induced by middle cerebral artery occlusion were analyzed for correspondence with changes in brain water, cation concentrations, and Na+,K(+)-ATPase activity measured in vitro after 30 or 60 min of ischemia. In the ischemic hemisphere, signal intensity was increased at 30 min (p < 0.05 vs contralateral hemisphere) and further increased at 60 min. Na+,K(+)-ATPase activity was 34% lower in ischemic cortex and 40% lower in ischemic basal ganglia after 30 min (p < 0.05), but water content and Na+ and K+ concentrations were not significantly different between hemispheres. After 60 min, water content and Na+ concentration were increased, and both Na+,K(+)-ATPase activity and K+ concentration were decreased in the ischemic hemisphere (p < 0.05). These findings are consistent with the hypothesis that the early onset of signal hyperintensity in diffusion-weighted MR images may reflect cellular edema associated with impaired membrane pump function. Early in vivo detection and localization of potentially reversible ischemic cerebral edema may have important research and clinical applications.

Mechanisms of brain injury associated with partial and complete occlusion of the MCA in cat.

High-speed MR diffusion/perfusion imaging was performed to assess variable degree stenosis of the MCA and the formation of cytotoxic edema in a cat model of acute ischemia. Sodium transport was estimated in synaptosomes isolated from moderately perfused or non-perfused brain tissue. Complete MCA occlusion for 50-75 min produced a major disruption of brain sodium transport, whereas continued preservation of ion homeostasis and the activation of adaptive cell volume regulatory systems was associated with longer duration of moderate severity of ischemia. Preservation of neuronal ion homeostasis might be one of the main mechanisms contributing to the relative tolerance of the brain to moderate reductions in cerebral blood flow.

Severe brain edema associated with cumulative effects of hyponatremic encephalopathy and ischemic hypoxia.

Hyponatremia in cats produced brain edema, detectable by both magnetic resonance imaging (MRI) and increased brain water, with a compensatory decrease of brain sodium. Sodium transport was measured in synaptosomes from hyponatremic cat cerebral cortex. The sodium efflux via Na(+)-K(+)-ATPase was significantly higher (144%) than control, while sodium influx via the Na+/H+ antiporter was significantly decreased (74%). Both responses tend to decrease brain intracellular sodium and thus, brain cell osmolality. Ischemia following unilateral middle cerebral artery occlusion also resulted in brain edema. However, the efflux of sodium via both Na(+)-K(+)-ATPase and sodium channels actually decreased, both maladaptive responses. Furthermore, when ischemia was superimposed upon hyponatremia, all of the cerebral adaptive changes which had been induced by hyponatremia alone were rendered ineffective. This resulted in further elevations of brain water and sodium. Hyponatremia superimposed upon ischemia thus worsens the brain edema associated with ischemia alone. Thus, ischemia impairs the ability of the brain to adapt to hyponatremia, probably by eliminating the compensatory mechanisms of brain sodium transport initiated by hyponatremia.

Iron-dextran as a magnetic susceptibility contrast agent: flow-related contrast effects in the T2-weighted spin-echo MRI of normal rat and cat brain.

Iron-dextran (1 mmol Fe/kg) was used as an intravascular, paramagnetic contrast agent in rat and cat brain in conventional spin-echo T2-weighted (TR 2800/TE 100) 1H magnetic resonance imaging. The resulting images displayed differential decreases (30-50%) in intensity whose pattern was similar to that obtained with the superparamagnetic particulate iron oxide AMI-25 (0.18 mmol Fe/kg). Postcontrast images displayed improved anatomic detail, and contrast effects were observed to be greater in cortical and subcortical gray matter than in adjacent white matter. Intravenous injection of acetazolamide after administration of iron-dextran caused a small additional decrease in image intensity. Measurement of whole blood and plasma at 5 min postinjection of either contrast agent revealed significant increases in their volume magnetic susceptibilities. The contrast effect appears to be related to magnetic susceptibility changes brought about by the iron-dextran; it has both blood volume and blood flow components. The static model of magnetic susceptibility effects in brain capillaries is modified to include bolus flow of erythrocytes, providing a mechanism for the observed flow effects.

Anisotropy in diffusion-weighted MRI.

Diffusional anisotropy of water protons, induced by nonrandom, directional barriers which hinder or retard water motion, is measurable by MRI. Faster water diffusion was observed when the diffusion-sensitizing gradient direction paralleled the long axes of white matter tracts, indicative of fewer barriers to water motion. Diffusion perpendicular to this axis was as much as four times slower. Anisotropy was seen pre- and postmortem in all axial, sagittal, and coronal planes, with and without cardiac gating. Ordering has also been observed in feline optic nerve and in human peripheral nerves. Utilization of this technique can greatly improve understanding and assessment of demyelinating disorders, of white matter infarcts and neoplasms, and of neonatal brain and spinal cord development.

MR imaging of the brain in patients with diabetes insipidus.

Diabetes insipidus is a clinical syndrome characterized by the excretion of copious volumes of dilute urine combined with persistent intake of abnormally large quantities of fluid. There are two general forms of the disease, central (vasopressin deficient) and nephrogenic (vasopressin resistant). Diabetes insipidus of central origin most often results from lesions in the hypothalamic-neurohypophyseal axis. Twenty-six cases of central diabetes insipidus were evaluated with the use of high-field-strength MR imaging. A wide variety of precipitating conditions were found, including Langerhans cell histiocytosis, neoplasia, trauma, and infection. A thickened pituitary infundibulum was seen in most patients, and an absence of high intensity signal in the posterior pituitary lobe on T1-weighted images was seen in every case. Analysis of stalk morphology; associated brain findings; and correlation with the patient's age, sex, history, and radiographs of other body parts improved diagnostic specificity. When combined with clinical information, MR imaging is able to provide a specific diagnosis in almost all cases of central diabetes insipidus.

The effect of phospholipid vesicles on the NMR relaxation of water: an explanation for the MR appearance of the neurohypophysis?

The normal neurohypophysis is hyperintense relative to brain and adenohypophysis on T1-weighted MR images, but the signal is not chemically shifted with respect to water. The source of the hyperintense MR signal in the normal neurohypophysis has been the subject of recent controversy. To date, an adequate biophysical explanation for the unusual imaging properties of the neurohypophysis has not been found. The purpose of this study was to investigate the effect of two chemical components of the neurohypophysis, phospholipids and vasopressin, on the MR signal. We synthesized phospholipid vesicles of the same size as those found in the neurohypophysis (100-200 nm) and quantitatively measured T1, T2, and chemical shift in a spectrometer at concentrations of 0-250 mg/ml of phospholipid. Imaging of the test materials was performed on a 1.5-T whole-body MR system using T1-weighted images, T2-weighted images, reduced bandwidth, and fat suppression techniques. The experiment was also performed with saline buffer, mineral oil, vasopressin, and vasopressin incorporated into the core of the phospholipid vesicles. We found that a solution containing phospholipid vesicles has T1 and T2 characteristics analogous to the neurohypophysis and that this solution exhibits a single peak that is not chemically shifted with respect to water. Vasopressin had no effect on the signal, neither in solution nor in the vesicles. We conclude that phospholipid acts as a relaxation enhancer of water protons and that the MR characteristics of the phospholipid vesicles can account for the observed MR properties of the neurohypophysis.

Thickened pituitary stalk on MR images in patients with diabetes insipidus and Langerhans cell histiocytosis.

The MR images of four female patients with acute onset of central diabetes insipidus and pathologically confirmed Langerhans cell histiocytosis were evaluated retrospectively for evidence of lesions in the hypothalamic-pituitary axis. The examinations were conducted on a 1.5-T MR system with thin-section sagittal and coronal T1-weighted (short TR/short TE) and T2-weighted (long TR/long TE) images. Three patients underwent T1-weighted MR after IV administration of gadopentetate dimeglumine. Compared with 20 normal subjects who were evaluated with the same MR protocol, three of the four patients had a symmetrically thickened pituitary stalk that demonstrated homogeneous signal enhancement following contrast administration. The high signal intensity of the posterior lobe, which was seen in normal subjects on T1-weighted sagittal images, was absent in all four patients. Two patients had associated abnormalities on either chest films or imaging studies of the temporal bone and two patients had isolated CNS Langerhans cell histiocytosis. The combination of a thickened pituitary stalk and absent posterior pituitary hyperintensity, while nonspecific for Langerhans cell histiocytosis, should nevertheless prompt further studies, such as chest films, bone scanning, or temporal bone CT, to attempt to narrow the differential diagnosis. Gadopentetate dimeglumine, in particular, may be a useful adjunct in the MR examination of the patient with diabetes insipidus.

Sex differences result in increased morbidity from hyponatremia in female rats.

The development of symptomatic hyponatremia in otherwise healthy young women can result in death or permanent brain damage. The reasons for the increased female susceptibility to complications from hyponatremia are, however, unclear. To determine whether mechanisms that normally defend the brain against damage from hyponatremia are less effective in females than males, we studied both sodium transport in the brains of hyponatremic male and female rats and the effects of parenteral arginine vasopressin on brain high-energy phosphate metabolism and intracellular pH. Basal sodium uptake in synaptosomes prepared from whole brain of females (2.20 nmol/mg protein) and males (2.98 nmol/mg protein) was not statistically different. In contrast, veratridine-stimulated sodium uptake in female brain was 8.20 nmol/mg protein, which was 86% greater (P less than 0.001) than the 6.12 nmol/mg protein observed for male brain. Additionally, sodium uptake between 5 and 60 s was significantly (P less than 0.001) greater in females than males. These data suggest that the Na+-K+-adenosinetriphosphatase (ATPase) pump function in female rat brain synaptosomes is less effective than in males. To determine whether arginine vasopressin, a peptide hormone that promotes water retention by the kidney, had any effects on cerebral energy metabolism, we performed phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) studies on the brain of normonatremic young adult male and female rats subjected to high (20 IU) peripheral doses of arginine vasopressin. We found decreased high-energy phosphate generation, elevated inorganic phosphate, and intracellular acidosis after arginine vasopressin administration in females but not males.(ABSTRACT TRUNCATED AT 250 WORDS)

Posterior pituitary ectopia: an MR feature of pituitary dwarfism.

Using high-field-strength, 1.5-T, high-resolution MR, we identified the following complex of neurohypophyseal abnormalities in each of five pituitary dwarfs: (1) severe hypoplasia or total absence of the infundibulum; (2) absence of the posterior pituitary bright spot in its normal location; and (3) a 3-8-mm tissue nodule at the median eminence exhibiting lipidlike signal on T1-weighted images. On the basis of its signal features and the clinical absence of diabetes insipidus in these patients, the median eminence nodule appears to represent an ectopic and functional posterior pituitary gland. We propose that this anatomic derangement is the end result of a localized defect of developmental origin, possibly ischemic in nature, and involving principally the infundibular stem. Thus, human growth hormone deficiency could result from perinatal disruption of the peri-infundibular hypophyseal portal system, which in turn impairs anterior pituitary function through deprivation of direct delivery of crucial hypothalamic-releasing factors. Finally, we suggest that the trophic influence of continued axonal neurosecretion at the median eminence engages proliferation of rest cell pituicytes; a process that induces formation of an ectopic and functional posterior pituitary gland, complete with its characteristic bright spot.

Posterior pituitary gland: appearance on MR images in normal and pathologic states.

T1-weighted magnetic resonance (MR) images of the pituitary gland and sella turcica routinely demonstrate a region of high signal intensity in the neurohypophysis. High-resolution MR imaging studies of the sella turcica in 200 subjects with a normal or abnormal sella were analyzed. The hyperintensity was found in the images of about 90% of healthy subjects and patients with microadenoma, in only 43% of patients with macroadenoma, and in 12% of patients with empty sellae. The signal was absent in several patients with functional or anatomic abnormalities of the hypothalamic-hypophyseal axis. It is concluded that the high signal intensity in the posterior lobe of the pituitary gland is present in most healthy individuals and that its absence in many patients with large intrasellar masses and empty sellae is due to compression of posterior lobe tissue. Its absence in diabetes insipidus further suggests a relationship between hyperintensity and the functional status of the hypothalamic-hypophyseal axis.