Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'.

The mouse neurological mutant 'motor endplate disease' (med) is characterized by early onset progressive paralysis of the hind limbs, severe muscle atrophy, degeneration of Purkinje cells and juvenile lethality. We have isolated a voltage-gated sodium channel gene, Scn8a, from the flanking region of a transgene-induced allele of med. Scn8a is expressed in brain and spinal cord but not in skeletal muscle or heart, and encodes a predicted protein of 1,732 amino acids. An intragenic deletion at the transgene insertion site results in loss of expression. Scn8a is closely related to other sodium channel alpha subunits, with greatest similarity to a brain transcript from the pufferfish Fugu rubripes. The human homologue, SCN8A, maps to chromosome 12q13 and is a candidate gene for inherited neurodegenerative disease.

Long base line interferometry: a new technique.

The technique of using magnetic-tape recorders and atomic frequency standards to operate two widely separated radio telescopes as a phase-coherent interferometer when the stations have no radio-frequency connecting link has been successfully tested at the National Research Council of Canada's Algonquin Radio Observatory.

Therapeutic angiogenesis with recombinant fibroblast growth factor-2 improves stress and rest myocardial perfusion abnormalities in patients with severe symptomatic chronic coronary artery disease.

BACKGROUND: We report the effects of the administration of recombinant fibroblast growth factor-2 (rFGF-2) protein on myocardial perfusion using single photon emission computed tomography imaging in humans with advanced coronary disease. METHODS AND RESULTS: A total of 59 patients with coronary disease that was not amenable to mechanical revascularization underwent intracoronary (n=45) or intravenous (n=14) administration of rFGF-2 in ascending doses. Changes in perfusion were evaluated at baseline and again at 29, 57, and 180 days after rFGF-2 administration. In this uncontrolled study, perfusion scans were analyzed by 2 observers who were blinded to patient identity and test sequence; scans were displayed in random order, with scans from nonstudy patients randomly interspersed to enhance blinding. Combining all dose groups, a reduction occurred in the per-segment reversibility score (reflecting the magnitude of inducible ischemia) from 1.7+/-0.4 at baseline to 1.1+/-0.6 at day 29 (P:<0.001), 1.2+/-0.7 at day 57 (P:<0.001), and 1.1+/-0.7 at day 180 (P:<0.001). The 37 patients with evidence of resting hypoperfusion had evidence of improved resting perfusion: their per-segment rest perfusion score of 1.5+/-0. 5 at baseline decreased to 1.0+/-0.8 at day 29 (P:<0.001), 1.0+/-0.8 at day 57 (P:=0.003), and 1.1+/-0.9 at day 180 (P:=0.11). CONCLUSIONS: These preliminary data suggest that the administration of rFGF-2 to patients with advanced coronary disease resulted in an attenuation of stress-induced ischemia and an improvement in resting myocardial perfusion; these findings are consistent with a favorable effect of therapeutic angiogenesis.

SPECT quantification: a simplified method of attenuation and scatter correction for cardiac imaging.

The quantitative and visual interpretation of SPECT myocardial perfusion images is limited by physical factors such as photon attenuation, Compton scatter, and finite resolution effects. A method of attenuation correction is described for use in nonhomogeneous media and applied to cardiac SPECT imaging. This method, termed multiplicative variable attenuation compensation (MVAC), uses tissue contours determined from segmentation of a transmission scan to assign a priori determined attenuation coefficients to different tissue regions of the transaxial images. An attenuation correction map is then constructed using a technique inspired by Chang's method that includes regionally dependent attenuation within the chest cavity and is applied after reconstruction by filtered backprojection. Scatter correction using the subtraction of a simultaneously acquired scatter window image enables the use of narrow beam attenuation coefficients. Experimental measurements to evaluate these methods were conducted for 201Tl and 99mTc SPECT using a homomorphic cardiac phantom. Finite resolution effects were included in the evaluation of results by computer simulation of the three-dimensional activity distribution. The correction methodology was shown to substantially improve both relative and absolute quantification of uniform and nonuniform regions of activity in the phantom's myocardial wall.

Measuring technetium-99m-MAG3 clearance with an improved camera-based method.

UNLABELLED: Because commercially available camera-based methods are not optimized, they fail to account for dose infiltration, table attenuation and correspondence between time of injection and starting the camera. We have developed a more optimized technique to calculate camera-based clearances and applied this technique in the design of a camera-based clearance method for 99mTc-MAG3. METHODS: Technetium-99m-MAG3 scintigraphy was performed in 20 patients who had varying degrees of renal function. Data were acquired posteriorly in supine patients at 2 sec/frame for 24 frames, 15 sec/frame for 16 frames and 30 sec/frame for 40 frames. Background correction was performed using an automated elliptical region of interest. Renal depth was estimated using improved regression equations and an empirically determined attenuation coefficient derived from phantom studies. Corrections were made for table attenuation and time discrepancies between dose injection and starting the camera. The percent injected dose in the kidney at 1-2, 1-2.5 and 2-3 min postinjection and the percent injected dose at those time periods corrected for body surface area were correlated with MAG3 clearance based on a single injection, two-compartment model. RESULTS: There was high correlation between the percent injected dose in the kidney at all three time periods and the multisample clearance. Correcting for body surface areas significantly improved the correlation coefficients. Consequently, regression equations were developed to predict multisample clearance based on percent dose and body surface area. CONCLUSION: The optimization features described in this method should improve precision when sequential studies are conducted in the same patient.

Technical aspects of myocardial SPECT imaging with technetium-99m sestamibi.

Most reports to date using single photon emission computed tomography (SPECT) with technetium-99m (Tc-99m) sestamibi have used acquisition parameters that were optimized for thallium-201. To fully utilize the superior imaging characteristics of Tc-99m sestamibi, there is a need to optimize the technical aspects of SPECT imaging for this agent. Performance can be enhanced through the careful selection of optimal radiopharmaceutical doses, imaging sequences, acquisition parameters, reconstruction filters, perfusion quantification methods and multidimensional methods for visualizing perfusion distribution. The current report describes theoretical considerations, phantom studies and preliminary patient results that have led to optimized protocols, developed at Emory University and Cedars-Sinai Medical Center, for same-day rest-stress studies, given existing instrumentation and recommended dose limits. The optimizations were designed to fit a low-dose-high-dose rest-stress same-day imaging protocol. A principal change in the acquisition parameters compared with previous Tc-99m sestamibi protocols is the use of a high-resolution collimator. The approach is being developed in both prone and supine positions. A new method for extracting a 3-dimensional myocardial count distribution has been developed that uses spherical coordinates to sample the apical region and cylindrical coordinates to sample the rest of the myocardium. New methods for visualizing the myocardial distribution in multiple dimensions are also described, with improved 2-dimensional, as well as 3- and 4-dimensional (3 dimensions plus time) displays. In the improved 2-dimensional display, distance-weighted and volume-weighted polar maps are used that appear to significantly improve the representation of defect location and defect extent, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Attenuation and scatter compensation in myocardial perfusion SPECT.

Nonuniform attenuation, Compton scatter, and limited, spatially varying resolution degrade both the qualitative and quantitative nature of myocardial perfusion SPECT. Physicians must recognize and understand the effects of these factors on myocardial perfusion SPECT for optimal interpretation and use of this important imaging technique. Recent developments in the design and implementation of compensation algorithms and transmission-based imaging promise to provide clinically realistic solutions to these effects and provide the framework for truly quantitative imaging. This achievement should improve the diagnostic accuracy and cost-effectiveness of myocardial perfusion SPECT.

Effects of myocardial wall thickness on SPECT quantification.

The effects of changing myocardial wall thickness in single photon emission computed tomography (SPECT) imaging are characterized, and a method which may be used to compensate for these effects is presented. The underlying principle is that the phenomena of attenuation, Compton scatter, and finite resolution can be separated and treated independently. Only finite resolution and its effects, along with a proposed method for correcting these effects, are addressed. A cardiac phantom with varying wall thickness (9-23 mm) was developed to characterize the dependence effects on (201)Tl myocardial SPECT images. Correction factors in the form of recovery coefficients have been developed with the use of a convolution simulation, and are shown to improve substantially the agreement of counts extracted from SPECT images of the phantom with the actual (201)Tl concentration. The degree of improvement, however, is markedly affected by external attenuation. Clinical application of this method will require corrections for attenuation and scatter or the development of regional recovery coefficients which include these effects.

A finite element model of skin deformation. III. The finite element model.

Skin flap design has traditionally been based on geometric models which ignore the elastic properties of skin and its subcutaneous attachments. This study reviews the theoretical and experimental mechanics of skin and soft tissues (I) and proposes a mathematical model of skin deformation based on the finite element method (III). Finite element technique facilitates the modeling of complex structures by analyzing them as an aggregate of smaller elements. This paper gives the results of an animal model developed to study the deformation and mechanical properties of skin, including its viscoelastic properties (hysteresis, creep, and stress relaxation). A new skin extensometer, constructed with digital stepper motors and controlled with a microcomputer, is described to measure these properties for both skin and its subcutaneous attachments. Deformation grids quantitated from photographs with a digitalizing tablet are presented, and computer software is introduced to standardize and analyze them (II). The mathematical model used to simulate wound closures such as the ellipse and rectangular advancement flap. In addition, a series of mathematical experiments performed to simulate deformation of a strip of skin are described; the relationships between the various elastic constants are investigated; and a comparison of these simulations with actual deformation is presented. Limitations of the model and areas for future investigation are discussed (III).

A finite element model for the design of local skin flaps.

A finite element model for the design of local skin flaps has been developed. This model, in spite of many limitations, provides an improved way to design local skin flaps. With improvements, the model could be used to plan surgical reconstructions in patients.

In-111 labeled octreotide imaging of a primary carcinoid lesion undetected by conventional imaging studies in a patient with "chronic pancreatitis".

This is a case report of a patient with an initial diagnosis of chronic pancreatitis who actually had metastatic carcinoid tumor. His symptoms of abdominal pain, weight loss, and diarrhea were manifestations of the large tumor bulk within the liver as well as carcinoid syndrome. Although abdominal CT scans showed multiple liver lesions, the primary lesion was not identified by conventional imaging studies. However, the mid-gut primary lesion was visualized on in-111 labeled octreotide scintigraphy; where the liver lesions were better delineated and seen to be separate from the normal pancreas when the Tc-99m sulfur colloid images were compared to the octreotide images.