Evaluation of left ventricular endocardial volumes and ejection fractions computed from gated perfusion SPECT with magnetic resonance imaging: comparison of two methods.

BACKGROUND: Two methods of computing left ventricular volumes and ejection fraction (EF) from 8-frame gated perfusion single photon emission computed tomography (SPECT) were compared with each other and with magnetic resonance (MR) imaging. METHODS AND RESULTS: Thirty-five subjects underwent 8-frame gated dual-isotope SPECT imaging and 12- to 16-frame gated MR imaging. Endocardial boundaries on short-axis MR images were hand traced by experts blinded to any SPECT results. Volumes and EF were computed with the use of Simpson's rule. SPECT images were analyzed for the same functional variables with the use of 2 automatic programs, Quantitative Gated SPECT (QGS) and the Emory Cardiac Toolbox (ECTb). The mean difference between MR and SPECT EF was 0.008 for ECTb and 0.08 for QGS. QGS showed a slight trend toward higher correlation for EF (r = 0.72, SE of the estimate = 0.08) than ECTb (r = 0.70, SE of the estimate = 0.09). For both SPECT methods, left ventricular volumes were similarly correlated with MR, although SPECT volumes were higher than MR values by approximately 30%. CONCLUSIONS: QGS and ECTb values of cardiac function computed from 8-frame gated perfusion SPECT correlate very well with each other and correlate well with MR. Averaged over all subjects, ECTb measurements of EF are not significantly different from MR values but QGS significantly underestimates the MR values.

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.

Two-point, timesaving method for measurement of gastric emptying with diagnostic accuracy comparable to that of the conventional method.

Solid-phase gastric emptying is linear. Therefore, the authors calculated gastric-emptying half-time, the time for half of the ingested solids or liquids to leave the stomach, with the conventional multiple-point method and the proposed two-point method (at 0 and 120 minutes) in retrospective and prospective studies of 50 patients each. The results showed excellent correlation. Results with the two-point method were comparable to those with the multiple-point method, and the two-point method substantially reduced technologist and camera times.

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.

Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.

The voltage-gated sodium channel SCN8A is associated with inherited neurological disorders in the mouse that include ataxia, dystonia, severe muscle weakness, and paralysis. We report the complete coding sequence and exon organization of the human SCN8A gene. The predicted 1980 amino acid residues are distributed among 28 exons, including two pairs of alternatively spliced exons. The SCN8A protein is evolutionarily conserved, with 98.5% amino acid sequence identity between human and mouse. Consensus sites for phosphorylation of serine/threonine and tyrosine residues are present in cyoplasmic loop domains. The polymorphic (CA)n microsatellite marker D12S2211, with PIC = 0.68, was isolated from intron 10C of SCN8A. Single nucleotide polymorphisms in intron 19 and exon 22 were also identified. We localized SCN8A to chromosome band 12q13.1 by physical mapping on a YAC contig. The cDNA clone CSC-1 was reported by others to be a cardiac-specific sodium channel, but sequence comparison demonstrates that it is derived from exon 24 of human SCN8A. The genetic information described here will be useful in evaluating SCN8A as a candidate gene for human neurological disease.

Multicenter trial validation of a camera-based method to measure Tc-99m mercaptoacetyltriglycine, or Tc-99m MAG3, clearance.

PURPOSE: To evaluate an improved camera-based method for calculating the clearance of technetium-99m mercaptoacetyltriglycine (MAG3) in a multicenter trial. MATERIALS AND METHODS: Tc-99m MAG3 scintigraphy was performed in 49 patients at three sites in the United States and Canada. The percentage of the injected dose of Tc-99m MAG3 in the kidney at 1-2, 1.0-2.5, and 2-3 minutes after injection was correlated with the plasma-based Tc-99m MAG3 clearances. The data were combined with the results obtained in 20 additional patients in a previously published pilot study. RESULTS: Regression models correlating the plasma-based Tc-99m MAG3 clearance with the percentage uptake in the kidney for each time interval were developed; there was no statistically significant difference among sites in the regression equations. Correction for body surface area statistically significantly (P < .005) improved the correlation coefficient for each time interval. For the 1.0-2.5-minute interval, the body surface area-corrected correlation coefficient for the four combined sites was .87, and it improved to .93 when one outlier was omitted from the analysis. Similar results were obtained with the other time intervals. Independent processing by two observers showed no clinically important differences in the percentage dose in the kidney or in relative function. CONCLUSION: An improved camera-based method to calculate the clearance of Tc-99m MAG3 was validated in a multicenter trial.

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.

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.

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.

Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15.

Homozygous transgenic mice from line A4 have an early-onset progressive neuromuscular disorder characterized by paralysis of the rear limbs, muscle atrophy, and lethality by 4 weeks of age. The transgene insertion site was mapped to distal chromosome 15 close to the locus motor endplate disease (med). The sequence of mouse DNA flanking the insertion site junctions was determined. A small (< 20 kb) deletion was detected at the insertion site, with no evidence of additional rearrangement of the chromosomal DNA. Noncomplementation of the transgene-induced mutation and med was demonstrated in a cross with medJ/+mice. The new allele is designated medTgNA4Bs (medtg). The homologous human locus MED was assigned to chromosome 12. Synaptotagmin 1 and contactin 1 were eliminated as candidate genes for the med mutation. The transgene-induced allele provides molecular access to the med gene, whose function is required for synaptic transmission at the neuromuscular junction and long-term survival of cerebellar Purkinje cells.

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.