Sympathetic and sensory innervation of brown adipose tissue.

The innervation of brown adipose tissue (BAT) by the sympathetic nervous system (SNS) is incontrovertible and, with its activation, functions as the principal, if not exclusive, stimulator of BAT thermogenesis. The parasympathetic innervation of BAT only appears in two minor BAT depots, but not in the major interscapular BAT (IBAT) depot. BAT thermogenesis is triggered by the release of norepinephrine from its sympathetic nerve terminals, stimulating ß3-adrenoceptors that turns on a cascade of intracellular events ending in activation of uncoupling protein-1 (UCP-1). BAT also has sensory innervation that may function to monitor BAT lipolysis, a response necessary for activation of UCP-1 by fatty acids, or perhaps responding in a feedback manner to BAT temperature changes. The central sympathetic outflow circuits ultimately terminating in BAT have been revealed by injecting the retrograde viral transneuronal tract tracer, pseudorabies virus, into the tissue; moreover, there is a high degree of colocalization of melanocortin 4-receptor mRNA on these neurons across the neural axis. The necessary and sufficient central BAT SNS outflow sites that are activated by various thermogenic stimuli are not precisely known. In a chronic decerebration procedure, IBAT UCP-1 gene expression can be triggered by fourth ventricular injections of melanotan II, the melanocortin 3/4 receptor agonist, suggesting that there is sufficient hindbrain neural circuitry to generate thermogenic responses with this stimulation. The recent recognition of BAT in normal adult humans suggests a potential target for stimulation of energy expenditure by BAT to help mitigate increased body fat storage.

Central melanocortin stimulation increases phosphorylated perilipin A and hormone-sensitive lipase in adipose tissues.

Norepinephrine (NE) released from the sympathetic nerves innervating white adipose tissue (WAT) is the principal initiator of lipolysis in mammals. Central WAT sympathetic outflow neurons express melanocortin 4-receptor (MC4-R) mRNA. Single central injection of melanotan II (MTII; MC3/4-R agonist) nonuniformly increases WAT NE turnover (NETO), increases interscapular brown adipose tissue (IBAT) NETO, and increases the circulating lipolytic products glycerol and free fatty acid. The WAT pads that contributed to this lipolysis were inferred from the increases in NETO. Because phosphorylation of perilipin A (p-perilipin A) and hormone-sensitive lipase are necessary for NE-triggered lipolysis, we tested whether MTII would increase these intracellular markers of lipolysis. Male Siberian hamsters received a single 3rd ventricular injection of MTII or saline. Trunk blood was collected at 0.5, 1.0, and 2.0 h postinjection from excised inguinal, retroperitoneal, and epididymal WAT (IWAT, RWAT, and EWAT, respectively) and IBAT pads. MTII increased circulating glycerol concentrations at 0.5 and 1.0 h, whereas free fatty acid concentrations were increased at 1.0 and 2.0 h. Western blot analysis showed that MTII specifically increased p-perilipin A and hormone-sensitive lipase only in fat pads that previously had MTII-induced increases in NETO. Phosphorylation increased in IWAT at all time points and IBAT at 0.5 h, but not RWAT or EWAT at any time point. These results show for the first time in rodents that p-perilipin A can serve as an in vivo, fat pad-specific indictor of lipolysis and extend our previous findings showing that central melanocortin stimulation increases WAT lipolysis.

Sensory characteristics and consumer acceptability of fermented soybean paste (Doenjang).

UNLABELLED: This study was conducted to examine the sensory profiles of fermented soybean paste (Doenjang), to understand consumers' acceptability of different types of Doenjang samples and to identify the sensory characteristics that drive consumer acceptability of Doenjang products. Descriptive analysis and consumer acceptability test were conducted for 7 different types of Doenjang samples. The samples included 2 types of Doenjang made by either traditional or commercially modified methods. For the descriptive analysis, 8 trained panelists developed and evaluated 31 descriptors. There were significant differences in all 31 attributes among the samples. Principal component analysis was also performed to summarize the sensory characteristics of the samples. In consumer testing, 200 consumers evaluated the acceptability of Doenjang samples. Significant differences in consumer acceptability were observed among the samples. The consumers preferred the Doenjang samples manufactured using a commercially modified method. In overall point of view, most consumers liked the Doenjang samples that had strong "sweet" and "MSG (monosodium glutamate)" tastes. It appears that "sweet" and "MSG" tastes are the drivers of liking for Doenjang. "Salty" taste, "meju,""traditional Korean soy sauce," and "fermented fish" odor/flavors seem to be the drivers of disliking for Doenjang. Cluster analysis identified 3 subconsumer segments sharing a common preference pattern for the 7 samples within a cluster. The results showed that each consumer cluster preferred different Doenjang samples. External preference mapping was performed to establish the relationships between the sensory attributes and consumer acceptability in each cluster. PRACTICAL APPLICATION: Consumption of the fermented soybean products is gradually expanding around the world, due to their various health benefits. Therefore, understanding sensory characteristics and consumer acceptability of Doenjang are becoming increasingly important. The intense and complex flavor characteristics of Doenjang make it difficult to obtain a comprehensive sensory profiling and drivers of liking. The finding of this study can be applied to development of a new product that has better consumer acceptability. Also this study can be a useful and effective guideline to researchers who intend to examine the sensory characteristics and consumer acceptability of fermented soybean pastes.

Sensory and sympathetic nervous system control of white adipose tissue lipolysis.

Circulating factors are typically invoked to explain bidirectional communication between the CNS and white adipose tissue (WAT). Thus, initiation of lipolysis has been relegated primarily to adrenal medullary secreted catecholamines and the inhibition of lipolysis primarily to pancreatic insulin, whereas signals of body fat levels to the brain have been ascribed to adipokines such as leptin. By contrast, evidence is given for bidirectional communication between brain and WAT occurring via the sympathetic nervous system (SNS) and sensory innervation of this tissue. Using retrograde transneuronal viral tract tracers, the SNS outflow from brain to WAT has been defined. Functionally, sympathetic denervation of WAT blocks lipolysis to a variety of lipolytic stimuli. Using anterograde transneuronal viral tract tracers, the sensory input from WAT to brain has been defined. Functionally, these WAT sensory nerves respond electrophysiologically to increases in WAT SNS drive suggesting a possible neural negative feedback loop to regulate lipolysis.

Short photoperiod-induced decrease of histamine H3 receptors facilitates activation of hypothalamic neurons in the Siberian hamster.

Nonhibernating seasonal mammals have adapted to temporal changes in food availability through behavioral and physiological mechanisms to store food and energy during times of predictable plenty and conserve energy during predicted shortage. Little is known, however, of the hypothalamic neuronal events that lead to a change in behavior or physiology. Here we show for the first time that a shift from long summer-like to short winter-like photoperiod, which induces physiological adaptation to winter in the Siberian hamster, including a body weight decrease of up to 30%, increases neuronal activity in the dorsomedial region of the arcuate nucleus (dmpARC) assessed by electrophysiological patch-clamping recording. Increased neuronal activity in short days is dependent on a photoperiod-driven down-regulation of H3 receptor expression and can be mimicked in long-day dmpARC neurons by the application of the H3 receptor antagonist, clobenproprit. Short-day activation of dmpARC neurons results in increased c-Fos expression. Tract tracing with the trans-synaptic retrograde tracer, pseudorabies virus, delivered into adipose tissue reveals a multisynaptic neuronal sympathetic outflow from dmpARC to white adipose tissue. These data strongly suggest that increased activity of dmpARC neurons, as a consequence of down-regulation of the histamine H3 receptor, contributes to the physiological adaptation of body weight regulation in seasonal photoperiod.

Thematic review series: adipocyte biology. Sympathetic and sensory innervation of white adipose tissue.

During our study of the reversal of seasonal obesity in Siberian hamsters, we found an interaction between receptors for the pineal hormone melatonin and the sympathetic nervous system (SNS) outflow from brain to white adipose tissue (WAT). This ultimately led us and others to conclude that the SNS innervation of WAT is the primary initiator of lipid mobilization in these as well as other animals, including humans. There is strong neurochemical (norepinephrine turnover), neuroanatomical (viral tract tracing), and functional (sympathetic denervation-induced blockade of lipolysis) evidence for the role of the SNS in lipid mobilization. Recent findings suggest the presence of WAT sensory innervation based on strong neuroanatomical (viral tract tracing, immunohistochemical markers of sensory nerves) and suggestive functional (capsaicin sensory denervation-induced WAT growth) evidence, the latter implying a role in conveying adiposity information to the brain. By contrast, parasympathetic nervous system innervation of WAT is characterized by largely negative neuroanatomical evidence (viral tract tracing, immunohistochemical and biochemical markers of parasympathetic nerves). Functional evidence (intraneural stimulation and in situ microdialysis) for the role of the SNS innervation in lipid mobilization in human WAT is convincing, with some controversy regarding the level of sympathetic nerve activity in human obesity.

CNS sympathetic outflow neurons to white fat that express MEL receptors may mediate seasonal adiposity.

Many animals show seasonal changes in adiposity that are triggered by changes in the photoperiod. For example, in short "winterlike" days, the nocturnal duration of pineal melatonin (MEL) secretion increases ultimately resulting in body fat decreases by Siberian hamsters. These decreases in body fat are mediated through increases in the sympathetic drive on white adipose tissue (WAT). The central nervous system (CNS) origins of the sympathetic outflow from brain to WAT include the suprachiasmatic nucleus (SCN), an area necessary for the reception of season-encoded MEL signals in Siberian hamsters. Therefore, we tested whether SCN neurons that are part of the sympathetic outflow to WAT also express MEL receptors (MEL(1a)). This was accomplished by labeling the sympathetic outflow from brain to WAT using a transsynaptic retrograde tract tracer, the pseudorabies virus (PRV), injected into inguinal WAT combined with labeling of brain MEL(1a) receptors using in situ hybridization. We found PRV-labeled neurons that also expressed MEL(1a)-receptor mRNA in several brain regions including the SCN. Thus the increased duration of MEL secretion in short days may increase MEL(1a)-receptor stimulation that, in turn, increases the sympathetic drive on WAT, thereby increasing lipolysis and decreasing adiposity.

SCN efferents to peripheral tissues: implications for biological rhythms.

The suprachiasmatic nucleus (SCN) is the principal generator of circadian rhythms and is part of an entrainment system that synchronizes the animal with its environment. Here, we review the possible communication of timing information from the SCN to peripheral tissues involved in regulating fundamental physiological functions as revealed using a viral, transneuronal tract tracer, the pseudorabies virus (PRV). The sympathetic nervous system innervation of the pineal gland and the sympathetic outflow from brain to white adipose tissue were the first demonstrations of SCN-peripheral tissue connections. The inclusion of the SCN as part of these and other circuits was the result of lengthened postviral injection times compared with those used previously. Subsequently, the SCN has been found to be part of the sympathetic outflow from the brain to brown adipose tissue, thyroid gland, kidney, bladder, spleen, adrenal medulla, and perhaps the adrenal cortex. The SCN also is involved in the parasympathetic nervous system innervation of the thyroid, liver, pancreas, and submandibular gland. Individual SCN neurons appear connected to more than one autonomic circuit involving both sympathetic and parasympathetic innervation of a single tissue, or sympathetic innervation of two different peripheral tissues. Collectively, the results of these PRV studies require an expansion of the traditional roles of the SCN to include the autonomic innervation of peripheral tissues and perhaps the modulation of neuroendocrine systems traditionally thought to be controlled solely by hypothalamic stimulating/inhibiting factors.

Renal kallikrein excretion: role of ethnicity, gender, environment, and genetic risk of hypertension.

BACKGROUND AND OBJECTIVE: Alterations in renal kallikrein excretion are well-described in hypertension, and kallikrein excretion may predict risk of developing hypertension, but kallikrein excretion has not been directly compared across several ethnic strata, nor have the effects of ethnicity, gender, environment, and genetic risk of hypertension been simultaneously considered as determinants of kallikrein. METHODS: We investigated determinants of kallikrein excretion in a cross-section of n = 204 normotensive subjects stratified by ethnicity (119 Caucasian, 33 African-American, 52 Asian), gender (109 men, 95 women), environment (spontaneous electrolyte intake/excretion), and heredity (genetic risk (family history) of hypertension). Results were interpreted by analysis of variance (with Bonferroni post hoc comparison corrections), analysis of covariance, multiple linear regression, and maximum likelihood. RESULTS: Urinary kallikrein activity varied substantially (F = 5.30, P = 0.006) across the three ethnic groups, with African-American values approximately 50% lower than Caucasian (P = 0.005) or Asian (P = 0.02). Ethnicity and gender (T = 3.24, P = 0.001) had independent effects on kallikrein, with women excreting approximately 50% more kallikrein than men, regardless of ethnicity. Subjects at genetic risk of hypertension were over-represented (P = 0.048) in the lower stratum of a bimodal distribution of kallikrein excretion (chi-square = 29.6, P < 0.001). Potassium excretion was diminished in African-Americans (P < 0.001 to P = 0.002), and in a multivariate analysis, potassium excretion was the strongest correlate of kallikrein excretion (T = 4.10, P = 0.0001). In a subset of Caucasian and African-American individuals, African-Americans exhibited diminished excretion of not only kallikrein and potassium, but also aldosterone (P = 0.003), suggesting a mechanistic link between potassium and kallikrein excretion in their ethnic variations. CONCLUSIONS: Kallikrein excretion is influenced by several independent determinants, both hereditary (gender, ethnicity, and genetic risk of hypertension) and environmental (potassium intake and excretion). Ethnicity and environment may interact uniquely to influence kallikrein, as demonstrated by the case of African-Americans with diminutions of both kallikrein and potassium excretion. These results suggest a mechanism whereby kallikrein excretion is diminished in African-Americans, as well as therapeutic strategies to correct this deficiency. Finally, the identified determinants of kallikrein excretion will require analytic adjustment during genetic studies of this 'intermediate phenotype' in hypertension. Journal of Human Hypertension (2000) 14, 461-468

Co-expression of melatonin (MEL1a) receptor and arginine vasopressin mRNAs in the Siberian hamster suprachiasmatic nucleus.

Durational melatonin signals, cued by the photoperiod and generated by the pineal gland, are processed in the brain to induce seasonally appropriate physiological and behavioural adaptations. The melatonin receptor subtype MEL1a (also known as mt1) appears to regulate seasonal responses. Single label in situ hybridization for MEL1a receptor mRNA revealed labelled cells in several brain regions of Siberian hamsters, including the suprachiasmatic nucleus, the paraventricular nucleus of the thalamus, and the reuniens nucleus of the thalamus. To characterize suprachiasmatic nucleus cells containing MEL1a receptor mRNA, we used 35S-labelled cRNA probes for MEL1a receptor mRNA in combination with digoxigenin-labelled cRNA probes for vasopressin, somatostatin, or orphan retinoid Z receptor beta (RZRbeta; a putative nuclear melatonin receptor). Cells in the suprachiasmatic nucleus that contained MEL1a receptor mRNA also contained mRNAs for vasopressin and RZRbeta, but not for somatostatin. These data suggest that suprachiasmatic nucleus vasopressin cells may respond to melatonin signals, raising the possibility that suprachiasmatic nucleus vasopressin output mediates some of the effects of melatonin on seasonal or circadian responses.

CNS origins of the sympathetic nervous system outflow to brown adipose tissue.

Brown adipose tissue (BAT) plays a critical role in cold- and diet-induced thermogenesis. Although BAT is densely innervated by the sympathetic nervous system (SNS), little is known about the central nervous system (CNS) origins of this innervation. The purpose of the present experiment was to determine the neuroanatomic chain of functionally connected neurons from the CNS to BAT. A transneuronal viral tract tracer, Bartha's K strain of the pseudorabies virus (PRV), was injected into the interscapular BAT of Siberian hamsters. The animals were killed 4 and 6 days postinjection, and the infected neurons were visualized by immunocytochemistry. PRV-infected neurons were found in the spinal cord, brain stem, midbrain, and forebrain. The intensity of labeled neurons in the forebrain varied from heavy infections in the medial preoptic area and paraventricular hypothalamic nucleus to few infections in the ventromedial hypothalamic nucleus, with moderate infections in the suprachiasmatic and lateral hypothalamic nuclei. These results define the SNS outflow from the brain to BAT for the first time in any species.

Dorsocaudal SCN microknife-cuts do not block short day responses in Siberian hamsters given melatonin infusions.

Siberian hamsters (Phodopus sungorus sungorus) undergo photoperiod-induced physiological and behavioral adaptations. These adaptations, including changes in reproductive and metabolic status, are triggered by the pineal gland through the nocturnal secretion of its principal hormone, melatonin. The possible CNS sites of melatonin action determined through radiolabeled melatonin binding include the paraventricular and reuniens nuclei of the thalamus and the suprachiasmatic nucleus (SCN). However, we do not know the mechanisms and circuitry involved in the transmission of melatonin signals. Bilateral electrolytic lesions of the SCN (SCNx) block the responses to short day-like (long duration) melatonin signals delivered daily via the timed infusion paradigm, suggesting that the SCN receives and transmits short-day melatonin signals. The purpose of the present experiment was to answer the following question: are short-day melatonin signals transmitted to other brain structures from the SCN through its dorsomedial/dorsocaudal fiber projections? Pinealectomized adult male hamsters given horizontal knife cuts (kc) just dorsocaudal to the SCN (SCN-kc), sham-kc, or SCNx were given daily subcutaneous short day-like melatonin infusions via the timed infusion paradigm for 6 weeks. Only the hamsters given SCNx exhibited long day-like gonadal, epididymal fat pad, and body masses. Therefore, short day melatonin signals received by the SCN were not transmitted to other areas of the central nervous system through SCN efferents projecting dorsomedially or dorsocaudally.

Chronic mesenteric ischemia: use of in vivo MR imaging measurements of blood oxygen saturation in the superior mesenteric vein for diagnosis.

PURPOSE: To determine if dogs and humans with chronic mesenteric ischemia demonstrate a decrease in the percentage of oxygenated hemoglobin (%HbO2) in the superior mesenteric vein (SMV) after a meal. MATERIALS AND METHODS: In 10 dogs, ameroid rings were surgically implanted around the superior mesenteric arteries to create gradual stenosis. Pre- and postoperative angiograms and pre- and postprandial magnetic resonance (MR) oximetry measurements of the SMV %HbO2, with flow-independent T2 measurements of venous blood, were obtained at different times. In 10 patients with atherosclerotic disease and six patients with symptomatic chronic mesenteric ischemia, the same measurements were obtained after at least 6 hours of fasting and at 15, 35, and 45 minutes after ingestion of a liquid nutritional supplement. RESULTS: In seven dogs, the postprandial SMV %HbO2 increased an average of 2.5% +/- 0.8 before surgery and decreased an average of 6.3% +/- 2.1 when hemodynamically significant (>70%) stenosis of the superior mesenteric artery developed 7-14 days after surgery. In the 10 patients without ischemia, the SMV %HbO2 increased by 4.6% +/- 0.6, whereas in the symptomatic patients a postprandial decrease of 8.8% +/- 0.7 occurred (P < .0001). CONCLUSION: Measurement of the SMV %HbO2 with MR oximetry is a promising test for diagnosis of chronic mesenteric ischemia.

MRI of pulmonary embolism using Gd-DTPA-polyethylene glycol polymer enhanced 3D fast gradient echo technique in a canine model.

This study was to evaluate the accuracy of MR angiography (MRA) using a Gd-DTPA-polyethylene glycol polymer (Gd-DTPA-PEG) with a 3D fast gradient echo (3D fgre) technique in diagnosing pulmonary embolism in a canine model. Pulmonary emboli were created in six mongrel dogs (20-30 kg) by injecting tantalum oxide-doped autologous blood clots into the femoral veins via cutdowns. MRI was performed with a 1.5 T GE Signa imager using a 3D fgre sequence (11.9/2.3/15 degrees) following intravenous injection of 0.06 mmol Gd/kg of Gd-DTPA-PEG. The dogs were euthanized and spiral CT of the lungs were then obtained on the deceased dogs. The MRI images were reviewed independently and receiver-operating-characteristic (ROC) curves were used for statistical analysis using spiral CT results as the gold standard. The pulmonary emboli were well visualized on spiral CT. Out of 108 pulmonary segments in the six dogs, 24 contained emboli >2 mm and 27 contained emboli < or = 2 mm. With unblinded review, MRI detected 79% of emboli >2 mm and only 48% of emboli < or = 2 mm. The blinded review results were significantly worse. Gd-DTPA-PEG enhanced 3D fgre MRI is potentially able to demonstrate pulmonary embolism with fairly high degree of accuracy, but specialized training for the interpretations will be required.

In vivo magnetic resonance evaluation of blood oxygen saturation in the superior mesenteric vein as a measure of the degree of acute flow reduction in the superior mesenteric artery: findings in a canine model.

RATIONALE AND OBJECTIVES: The authors tested the hypothesis that changes in oxygen saturation (%HbO2) in the superior mesenteric vein (SMV), as measured with in vivo magnetic resonance (MR) oximetry, correlate with the degree of acute superior mesenteric artery (SMA) flow reduction. METHODS: Ten mongrel dogs were studied. A catheter was inserted into the SMV, and a perivascular ultrasonic flow probe and an adjustable mechanical occluder were placed around the SMA. MR oximetry was carried out at the resting state and after the SMA was constricted to predetermined levels (0%-75% of initial flow). In seven dogs, SMV blood samples were obtained immediately before and after each MR measurement; %HbO2 was measured simultaneously by using an oximeter. With linear regression analysis, the SMV %HbO2 measurements obtained at MR imaging were compared with those obtained at oximetry. With a logistic model, MR imaging changes in SMV %HbO2 were compared with the degree of SMA flow reduction. RESULTS: SMV %HbO2 measurements obtained with MR imaging correlated well with those obtained with oximetry (r = .97). Changes in SMV %HbO2 measured at MR imaging also correlated well with the degree of SMA flow reduction, as determined with a logistic model (P = .01). CONCLUSION: Noninvasive in vivo MR measurements of SMV %HbO2 can be used to determine the degree of acute SMA flow reduction with a high degree of accuracy in a canine model.

The effects of anterior hypothalamic lesions on short-day responses in Siberian hamsters given timed melatonin infusions.

The suprachiasmatic nucleus (SCN) of the hypothalamus is an area of dense 2-[125I]Iodomelatonin binding in Siberian hamsters (Phodopus sungorus sungorus) that is suggestive of a possible role in the reception and/or relaying of melatonin (MEL) signals. Indeed, in pinealectomized male Siberian hamsters given short day (SD) MEL signals (long-duration MEL infusions), lesions of the SCN (SCNx) block testicular regression and decreases in body and fat pad masses seen in identically treated hamsters with sham lesions (SCNs). In similar studies using Syrian hamsters (Mesocricetus auratus), anterior hypothalamic lesions (AHx), but not SCNx, blocked SD MEL signal-induced gonadal regression despite the similarity in the 2-[125I]Iodomelatonin binding pattern between the two species. The discrepancy between the ability of SCNx to block the reception of SD MEL signals between the two species is puzzling, given the similarity in the reproductive status of the Syrian and Siberian hamsters to systemically administered and timed MEL infusions. One possible way of reconciling the differences between these studies was that ancillary damage to areas neighboring the SCN, including the AH, may have occurred in our attempt to achieve complete SCNx in Siberian hamsters. Therefore, the purpose of the present study was to challenge AHx Siberian hamsters with SD MEL signals. Adult male hamsters were pinealectomized, fitted with subcutaneous catheters, and given daily timed infusions of MEL for 5 or 10 h (long day-like and short day-like, respectively) or the saline vehicle for 6 wk following bilateral electrolytic, or sham (AHs) lesions of the AH. Hamsters receiving 10 h MEL infusions that lacked evidence of anatomical or functional damage to the SCN showed SD-like gonadal regression, decreases in body and fat pad mass, and food intake similar to that observed in AHs animals. In contrast, 10 h MEL-infused SCNx hamsters did not exhibit SD-like responses, a finding confirming our previous report. These data suggest that interspecies differences exist between Syrian and Siberian hamsters in central nervous system sites and pathways involved in the reception/transmission of SD MEL signals.

Paramagnetic polymerized liposomes as new recirculating MR contrast agents.

We describe a well-tolerated blood pool contrast agent with extended recirculatory half-life based on paramagnetic polymerized liposomes (PPLs). PPLs were constructed from a new type of polymerizable lipid molecule that has a derivative of gadopentetate dimeglumine as the hydrophilic head group and diacetylene groups in the hydrophobic acyl chains, which cross-link when irradiated with ultraviolet (UV) light. Biodistribution, blood pool half-life, and MR image enhancement were determined for PPLs composed of 10% of the gadopentetate dimeglumine lipid and 90% of ditricosadiynoyl tricosadiynayl phosphatidylcholine (DAPC) at a dose of 0.015 mmol Gd+3/kg in rats. In T1-weighed MR images (TR/TE = 400/18 msec), an average signal enhancement of 34% in the kidneys and 20% in the liver was observed, which persisted for at least 90 minutes after administration of the PPLs. Biodistribution studies using radiolabeled PPLs confirmed that 80% of the injected dose remained in the blood pool after 2 hours. The half-life of elimination from the blood pool was 19 hours. The preparation was well tolerated in rats and produced similar MR contrast enhancement of the blood pool as produced by other liposome contrast agents. However, the half-life of PPL elimination from the blood pool was prolonged relative to other liposome systems.

Oxygen saturation of blood in the superior mesenteric vein: in vivo verification of MR imaging measurements in a canine model. Work in progress.

PURPOSE: To evaluate the accuracy of magnetic resonance (MR) imaging in estimating oxygen saturation of blood (%HbO2) in the superior mesenteric vein (SMV) of a canine model in vivo. MATERIALS AND METHODS: MR imaging was used to measure the T2 of blood in samples obtained via a catheter placed in the SMV in seven mongrel dogs. %HbO2 was measured with a reflectance oximeter. These measurements were obtained at the resting state, during superior mesenteric artery occlusion, and after reperfusion. MR imaging and oximeter measurements were then compared by using linear regression analysis. RESULTS: Refocusing intervals (tau 180) of 12 and 24 msec were used for 17 and 18 %HbO2 measurements with MR imaging, respectively. With tau 180 of 12 msec, there was an excellent correlation between MR imaging measurements and oximeter measurements (r = .969). The intercept was 5.3% and the slope was 0.959. With tau 180 of 24 msec, r = .953, the intercept was 15.4%, and the slope was 0.817. CONCLUSION: Estimates of %HbO2 in the SMV with MR imaging are accurate in the range of most clinical interest.

Simultaneous measurement of flow in the superior mesenteric vein and artery with cine phase-contrast MR imaging: value in diagnosis of chronic mesenteric ischemia. Work in progress.

PURPOSE: To evaluate the use of measurements of blood flow in the superior mesenteric vein (SMV) and superior mesenteric artery (SMA) simultaneously acquired with phase-contrast cine magnetic resonance (MR) imaging for diagnosing chronic mesenteric ischemia. MATERIALS AND METHODS: Simultaneous measurements of flow in the SMV and SMA were obtained in six healthy volunteers and eight patients with angiographically proved SMA stenosis (six asymptomatic, two symptomatic). Flow dynamics in both vessels were correlated with the degree of arterial disease seen at angiography and with the presence or absence of ischemic symptoms. RESULTS: Postprandial SMV and SMA flow increased substantially less in patients with atherosclerosis than in volunteers. Comparison of simultaneous SMV and SMA flow measurements provided more information about collateral flow to and from the mesenteric circulation than did either the SMV or SMA flow measurement alone. CONCLUSION: Simultaneous SMV and SMA flow measurement with cine phase-contrast MR imaging may be useful in diagnosing and understanding chronic mesenteric ischemia.