Bruce E. Hammer

NMR imaging of velocity profiles and velocity distributions in bead packs

Spatially resolved velocity profiles and spatially nonresolved velocity distributions of steady flow in a tube and bead packs were measured. Two different NMR experiments were used to measure velocity distributions. In one, the velocity histogram was calculated from spatially resolved velocity phase encoded images acquired in a 6 mm bead pack. In the other, a Fourier flow method was used to measure the velocity distribution directly in a 0.25 mm bead pack. Axial velocity profiles in the pore space of the 6 mm bead pack at Reynolds numbers of 14.9, 29.9, and 44.8 proved to be roughly parabolic, with maxima near the pore centers. Both NMR methods yielded the same dimensionless velocity distributions that contain negative as well as positive velocity components. The velocity distribution function derived from a bundle‐of‐tubes‐model accounts for the positive part of the velocity distribution.

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.J. Magn. Reson. Imaging 1999;9:596–603.

Use of a magnetic field to increase the spatial resolution of positron emission tomography

Detector geometry, spatial sampling, and more fundamentally, positron range and noncollinearity of annihilation photon emission define Positron Emission Tomography (PET) spatial resolution. In this paper, a strong magnetic field is used to constrain positron travel transverse to the field. Measurement of the spread function from a 500 microns diameter 68Ga impregnated resin bead shows a squeezing of the full width at half maximum (FWHM) by a factor of 1.0, 1.22, 1.42, and 2.05, at 0, 4.0, 5.0, and 9.4 Tesla, respectively. The full width at tenth maximum (FWTM) decreases by a factor of 1.0, 1.73, 2.09, and 3.20, at 0, 4.0, 5.0, and 9.0 Tesla, respectively. Acquiring a PET image in a magnetic field should significantly reduce resolution loss due to positron range.

Combined MRI-PET scanner: a Monte Carlo evaluation of the improvements in PET resolution due to the effects of a static homogeneous magnetic field

Positron emission tomography (PET) relies upon the detection of photons resulting from the annihilation of positrons emitted by a radiopharmaceutical. The combination of images obtained with PET and magnetic resonance imaging (MRI) have begun to greatly enhance the study of many physiological processes. A combined MRI-PET scanner could alleviate much of the spatial and temporal coregistration difficulties currently encountered in utilizing images from these complementary imaging modalities. In addition, the resolution of the PET scanner could be improved by the effects of the magnetic field. In this computer study, the utilization of a strong static homogeneous magnetic field to increase PET resolution by reducing the effects of positron range and photon noncollinearity was investigated, The results reveal that significant enhancement of resolution can be attained, For example, an approximately 27% increase in resolution is predicted for a PET scanner incorporating a 10-Tesla magnetic field. Most of this gain in resolution is due to magnetic confinement of the emitted positrons. Although the magnetic field does mix some positronium states resulting in slightly less photon noncollinearity, this reduction does not significantly affect resolution. Photon noncollinearity remains as the fundamental limiting factor of large PET scanner resolution.

Positron emission tomography within a magnetic field using photomultiplier tubes and lightguides

The spatial resolution of positron emission tomography (PET) improves when positron annihilation takes place in a strong magnetic field. In a magnetic field, the Lorentz force restricts positron range perpendicular to the field. Since positron annihilation occurs closer to its point of origin, the positron annihilation point spread function decreases. This was verified experimentally by measuring the spread function of positron annihilation from a 500 mm 68Ge bead imbedded in tissue-equivalent wax. At 5 T the spread function full width at half maximum (FWHM) and the full width at tenth maximum (FWTM) decrease by a factor of 1.42 and 2.09, respectively. Two NaI(Tl) scintillation crystals that interface to a pair of photomultiplier tubes (PMTS) through long lightguides detect positron annihilation at zero field and 5.0 T. Photomultiplier tubes, inoperable in strong magnetic fields, are functional if lightguides bring the photons produced by scintillators within the field to a minimal magnetic field. These tests also demonstrate techniques necessary for combining magnetic resonance imaging (MRI) and PET into one scanner.

Ringer's ethyl pyruvate in hemorrhagic shock and resuscitation does not improve early hemodynamics or tissue energetics

Reactive oxygen species (ROS) have been implicated in the pathogenesis of hemorrhagic shock. Ethyl pyruvate, a derivative of pyruvate and a proposed oxygen radical scavenger, is attractive as a possible resuscitation fluid. We investigated whether resuscitation with lactated Ringers (LR) containing ethyl pyruvate (REP) had any hemodynamic or tissue energetic benefits compared with LR alone for hemorrhagic shock. Hemorrhagic shock was induced in splenectomized pigs via inferior vena cava cannula. After 90 min of shock, animals were resuscitated in a stepwise fashion with LR or REP (30 mg/kg/dose, given as 1.5 mg/mL in LR) at 20 cc/kg/step for four steps. Data collected during this experiment included physiologic and hemodynamic parameters, near-infrared reflectance spectroscopy measurements of tissue hemoglobin oxygen (StO2) of the stomach, liver, and hind limb, and nuclear magnetic resonance phosphorus spectra of the liver and hind limb at each time point. In both resuscitative groups, heart rate, and lactate and pyruvate values increased during shock and began to drop toward baseline values during resuscitation. Mean arterial pressure, oxygen delivery, and oxygen consumption decreased during shock and increased toward baseline levels during the resuscitative process. There were no significant changes in physiologic parameters between the LR- and REP-resuscitated animals. There was a significantly lower stomach StO2 and hind limb cellular cytoplasmic pH during later resuscitative endpoints in REP-resuscitated animals. The clinical significance of these findings are unclear. There is no short-term hemodynamic or tissue energetic advantage to using REP as a resuscitation fluid when compared with LR. Long-term outcome studies are needed to further evaluate any potential benefits of use of REP in hemorrhagic shock.

Pancreas Oxygen Persufflation Increases ATP Levels as Shown by Nuclear Magnetic Resonance

BACKGROUND Islet transplantation is a promising treatment for type 1 diabetes. Due to a shortage of suitable human pancreata, high cost, and the large dose of islets presently required for long-term diabetes reversal; it is important to maximize viable islet yield. Traditional methods of pancreas preservation have been identified as suboptimal due to insufficient oxygenation. Enhanced oxygen delivery is a key area of improvement. In this paper, we explored improved oxygen delivery by persufflation (PSF), ie, vascular gas perfusion. METHODS Human pancreata were obtained from brain-dead donors. Porcine pancreata were procured by en bloc viscerectomy from heparinized donation after cardiac death donors and were either preserved by either two-layer method (TLM) or PSF. Following procurement, organs were transported to a 1.5-T magnetic resonance (MR) system for (31)P nuclear magnetic resonance spectroscopy to investigate their bioenergetic status by measuring the ratio of adenosine triphosphate to inorganic phosphate (ATP:P(i)) and for assessing PSF homogeneity by MRI. RESULTS Human and porcine pancreata can be effectively preserved by PSF. MRI showed that pancreatic tissue was homogeneously filled with gas. TLM can effectively raise ATP:P(i) levels in rat pancreata but not in larger porcine pancreata. ATP:P(i) levels were almost undetectable in porcine organs preserved with TLM. When human or porcine organs were preserved by PSF, ATP:P(i) was elevated to levels similar to those observed in rat pancreata. CONCLUSION The methods developed for human and porcine pancreas PSF homogeneously deliver oxygen throughout the organ. This elevates ATP levels during preservation and may improve islet isolation outcomes while enabling the use of marginal donors, thus expanding the usable donor pool.

Tissue energetics as measured by nuclear magnetic resonance spectroscopy during hemorrhagic shock

The defect in energy production in an organism during shock states may be related to the impairment of mitochondrial respiration early in shock. The aim of this study was to investigate the timing and degree of cellular energetic changes during hemorrhagic shock in real time. Instrumented, splenectomized swine were randomized to undergo hemorrhagic shock, induced by a 35% blood volume bleed, for 90 min with (n = 10) or without (n = 9) subsequent resuscitation. Resuscitated animals received shed blood in two increments followed by two normal saline boluses (20 mL/kg/bolus). Throughout experimentation, tissue phosphoenergetics of liver and skeletal muscle were monitored using 31P nuclear magnetic resonance (NMR) spectroscopy via NMR coils on the liver and hindlimb. Near-infrared spectroscopy probes were used to measure liver, stomach, and skeletal muscle oxyhemoglobin saturation (StO2). Hemorrhagic shock induced an increase in phosphomonoesters in skeletal muscle (baseline: 7.09%, 90 min: 9.94% (P < 0.05); expressed as percent total phosphorus). This increase resolved in animals receiving resuscitation (n = 10) but remained elevated in those in unresuscitated shock (n = 9). Inorganic phosphate levels increased and &bgr;ATP levels decreased significantly in the liver of animals in shock as compared with baseline. StO2 in skeletal muscle, stomach, and liver correlated with whole organism oxygen delivery (r2 = 0.356, 0.368, and 0.432, respectively). We conclude that hemorrhagic shock induces early elevation of phosphomonoesters in skeletal muscle, which correlates with the severity of shock. This implies an early transition to anaerobic glycolysis during hemorrhagic shock, which may be indicative of early mitochondrial dysfunction.

Effect of harvesting protocol on performance of a hollow fiber bioreactor

In this study, a bioreactor subject to Starling flow in closed shell batch harvest mode was compared to two forms of additional forced extracapillary (EC) space convection including EC circulation and EC cycling. Despite the presence of Starling flow as the dominant EC convection mechanism in the batch harvest system, the bioreactor start up was fairly good. However, the antibody productivity of the batch harvest system fell off rapidly after day 20 resulting in only 4.5 g of antibody produced. EC circulation with flow parallel to the fibers had a slightly better start up than the batch harvest. However, the antibody productivity also dropped after day 20 with EC circulation, resulting in only 7.5 g of antibody produced. EC cycling with flow both parallel and perpendicular to the fibers resulted in a start up similar to that of EC circulation. However, in contrast to the other two systems, antibody productivity in the EC cycling system was stable over the 60-day experiment resulting in the production of 23 g of antibody. These results demonstrate the importance of inducing the proper flow distribution in the EC space to allow consistent and stable production in hollow fiber bioreactors.

Persufflation Improves Pancreas Preservation When Compared With the Two-Layer Method

Islet transplantation is emerging as a promising treatment for patients with type 1 diabetes. It is important to maximize viable islet yield for each organ due to scarcity of suitable human donor pancreata, high cost, and the large dose of islets required for insulin independence. However, organ transport for 8 hours using the two-layer method (TLM) frequently results in low islet yields. Since efficient oxygenation of the core of larger organs (eg, pig, human) in TLM has recently come under question, we investigated oxygen persufflation as an alternative way to supply the pancreas with oxygen during preservation. Porcine pancreata were procured from donors after cardiac death and preserved by either TLM or persufflation for 24 hours and subsequently fixed. Biopsies collected from several regions of the pancreas were sectioned, stained with hematoxylin and eosin, and evaluated by a histologist. Persufflated tissues exhibited distended capillaries and significantly less autolysis/cell death relative to regions not exposed to persufflation or to tissues preserved with TLM. The histology presented here suggests that after 24 hours of preservation, persufflation dramatically improves tissue health when compared with TLM. These results indicate the potential for persufflation to improve viable islet yields and extend the duration of preservation, allowing more donor organs to be utilized.