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Lynne L Johnson

Publications and source records attributed to Lynne L Johnson.

16 recordsLinked to original sources
PubMed2006

Risk stratification with electrocardiographic-gated dobutamine stress technetium-99m sestamibi single-photon emission tomographic imaging: value of heart rate response and assessment of left ventricular function.

OBJECTIVES: The purpose of this research was to evaluate the significance of heart rate response to dobutamine and the assessment of left ventricular (LV) function during risk stratification of patients undergoing dobutamine stress myocardial perfusion imaging (DSMPI). BACKGROUND: Dobutamine stress myocardial perfusion imaging has been shown to effectively risk stratify highly selected patients. However, based on perfusion alone, patients with normal and abnormal tests have twice the risk as comparable patients with exercise testing. The added value of assessment of LV function and the heart rate response to dobutamine in risk stratification of these patients is unknown. METHODS: Follow-up information (cardiac death or non-fatal myocardial infarction) was obtained on 1,367 consecutive patients who underwent DSMPI due to inability to perform adequate exercise and contraindications to vasodilators. Perfusion images were interpreted using a 17-segment model. Abnormal perfusion and function were defined as: summed stress score > or =4 and ejection fraction <50%, respectively. RESULTS: Annualized event rates (AERs) were related to the extent/severity of perfusion defects and worsening LV function. A three-risk category model was constructed from combined assessment of perfusion and function, with AERs of 2.4% (both normal), 5.8% (discordant), and 11.3% (both abnormal); p < 0.001. Stress electrocardiogram (ECG) data added incremental value to myocardial perfusion alone but not to combined assessment of perfusion and function. Importantly, inability to achieve 85% of mean predicted heart rate was associated with worse outcomes and was an independent predictor of cardiac events. For patients in whom perfusion, function, and stress ECG response were normal, inability to achieve target heart rate was associated with significantly higher AER (1.5% vs. 3.4%, respectively, p = 0.021). CONCLUSIONS: In highly selected patients undergoing DSMPI, assessment of perfusion and function is effective in risk stratification. The stress ECG and heart rate response to dobutamine have prognostic value and should be incorporated into image interpretation so as to maximize risk stratification.

Aged↗
PubMed2006

Imaging experimental atherosclerotic lesions in ApoE knockout mice: enhanced targeting with Z2D3-anti-DTPA bispecific antibody and 99mTc-labeled negatively charged polymers.

UNLABELLED: In vivo molecular imaging may be improved if specific radioactivity at the target site could be increased while maintaining low background activity. Bispecific antibody complexes and (99m)Tc-labeled negatively charged chelating polymers that react specifically with the capture arm of the bispecific antibody complex were used to demonstrate the feasibility of imaging very small atherosclerotic lesions in ApoE knockout mice. METHODS: Left femoral artery denudation in ApoE(-/-) mice on a hyperlipidemic diet was used to induce accelerated atherosclerotic lesions. Approximately 40 microg of bispecific antibodies were injected intravenously after 2 wk of endothelial denudation. The next day, approximately 15.0 MBq (99m)Tc-DTPA-succinyl-polylysine (2 microg; DTPA is diethylenetriaminepentaacetic acid) were injected intravenously. RESULTS: In vivo gamma-images showed that lesions were observed unequivocally by 2-3 h. Sham-operated right femoral regions showed no radiotracer accumulation. Ex vivo gamma-scintillation counting corrected for sham-operated nonspecific activity and lesion mass showed that the mean lesion activity was 10.10 +/- 6.76 %ID/g (percentage injected dose per gram), whereas nonspecific human IgG bispecific control (NSB control) also corrected similarly was 0.939 +/- 0.877 %ID/g (P < 0.03). Atherosclerotic lesions were confirmed by immunohistochemical staining. Computer planimetry of immunohistograms showed the mean lesion size to be 2.64 +/- 2.46 mg. CONCLUSION: Use of bispecific antibody complexes and (99m)Tc-DTPA-succinyl-polylysine enabled in vivo visualization of very small atherosclerotic lesions in ApoE knockout mice.

Animals↗
PubMed2005

Smooth muscle cell proliferation index correlates with 111In-labeled antibody Z2D3 uptake in a transplant vasculopathy swine model.

UNLABELLED: Transplant vasculopathy is a major cause of morbidity and mortality in heart transplantation. The proliferation of coronary vascular smooth muscle cells is a hallmark of transplant vasculopathy. The goal of this study was to detect coronary vascular smooth muscle cell proliferation in a swine model by imaging regions of uptake of a monoclonal antibody (Z2D3) labeled with 111In. METHODS: Coronary-to-right carotid artery transplantation was performed in 10 Yucatan minipigs with coronary arteries from farm pigs as donors. In 5 of these experiments, the right carotid artery was also grafted to the left carotid artery as a homograft. In 1 farm pig, the left and right carotid arteries were switched. After 44 +/- 22 days (mean +/- SE), animals were injected with 5-bromo-2-deoxyuridine (BrDU) and 111In-Z2D3 F(ab')2. Approximately 24 h later, the pigs underwent planar and SPECT imaging. After the imaging session, the pigs were sacrificed and the vessels were removed. Ex vivo autoradiography of all grafts was performed. Next, the tissues were immersion fixed, paraffin embedded, sectioned, and stained for histologic or immunohistologic examination. Quantitative morphometry was performed. A smooth muscle cell proliferation index, calculated as (BrDU- and actin-stained cells/actin-stained cells) x 100, was correlated with in vivo and ex vivo radiotracer uptake. RESULTS: Patency or neovascularization was demonstrated in 10 of 10 allografts and 5 of 6 homografts. Ten of the scans were positive for focal tracer uptake in the neck in the area corresponding to the graft site, and 6 were negative. Actin- and BrDU-stained cells were seen in the media of allografts and in the recanalized lumen of occluded homografts. A smooth muscle cell proliferation index of 30 was used as a cutoff for scan positivity, on the basis of previous work. Analysis by the chi2 test indicated significant concordance (P < 0.01). Ex vivo vessel count ratios were significantly correlated with the smooth muscle cell proliferation index (r2 = 0.528, P < 0.01). CONCLUSION: The use of monoclonal antibody Z2D3 tagged with 111In allows the detection of proliferating smooth muscle cells and correlates with the intensity of cell proliferation. This diagnostic method could allow early noninvasive detection of transplant vasculopathy.

Animals↗
PubMed2005

99mTc-annexin V imaging for in vivo detection of atherosclerotic lesions in porcine coronary arteries.

UNLABELLED: We used a model of porcine coronary atherosclerosis characterized by smooth muscle cell apoptosis to test the hypothesis that apoptosis of cells in the vascular wall of coronary arteries can be detected on SPECT images using a technetium-labeled radiotracer that targets apoptosis. METHODS: Eleven juvenile male swine received a high-fat diet combined with injury to 22 coronary vessels. After 51 +/- 9 d (mean +/- SD), the animals underwent coronary angiography, were injected with 403.3 +/- 48.1 MBq of 99mTc-annexin V, underwent SPECT, and were sacrificed. The coronary arteries underwent autoradiography and well counting, and immunostaining was performed for alpha-actin, caspase, and macrophages. RESULTS: Atherosclerotic lesions were predominantly of American Heart Association class II. Thirteen of the 22 injured vessels showed focal uptake of 99mTc-annexin V in vivo (scan positive), and 9 injured vessels and all control vessels showed no focal uptake (scan negative). The count ratios of the injured vessels to the control vessels were 2.38 +/- 0.61 for scan-positive vessels and 1.27 +/- 0.23 for scan-negative vessels (P < 0.001). The percentages of injected dose for the scan-positive and scan-negative vessels were 1.73 +/- 0.83 x 10(-3) and 0.68 +/- 0.20 x 10(-3), respectively (P < 0.001). Immunohistopathologic examination found that the cells undergoing apoptosis were smooth muscle cells. The apoptotic index (caspase-positive cells to total cells) was 63% +/- 7% for scan-positive vessels and 16% +/- 10% for scan-negative vessels (P < 0.001). Both the count ratio of injured vessels to control vessels and the percentage injected dose correlated significantly with death rate by regression analysis. CONCLUSION: Annexin is a noninvasive method to identify plaque apoptosis in the coronary vessels.

Animals↗
PubMed2004

Hyperbaric oxygen solution infused into the anterior interventricular vein at reperfusion reduces infarct size in swine.

This study was designed to test the hypothesis that raising myocardial O2 via diffusion of a hyperbaric oxygen solution (AO) administered through the anterior interventricular vein (AIV) will reduce infarct size by reducing reperfusion injury associated with reduced neutrophil activation. In three pilot open-chest swine experiments, myocardial tissue Po2 was monitored using an oxygen probe during coronary occlusion (Occl) and reperfusion (Rep). One control experiment had no AIV infusion; a second control received arterial blood drawn from the femoral artery infused into the AIV during Rep. In a third open-chest experiment, AO mixed with arterial blood was infused through the AIV at Rep. In controls, tissue Po2 in the risk region (RR) rose early in Rep and then fell to Occl levels, whereas in AO-treated animals, myocardial Po2 remained above baseline. The following three groups of five swine then underwent 60 min of left anterior descending coronary artery Occl and Rep: 1) arterial blood infused at Rep as controls (Con), 2) AO infused beginning 30 min after Rep (AO 30 min), and 3) AO infused immediately at Rep (AO 0 min). There were no differences among the three groups in hemodynamics or myocardial blood flow during baseline (BL) or Occl or in RR size. However, endocardial blood flow was significantly higher in RR during Rep in AO 0 min vs. control and AO 30 min (P=0.01). Both infarct size (IS) as %heart and IS as %RR were lower in AO 0 min compared with Con and AO 30 min (P <0.01 for both), and myeloperoxidase values were lower for epicardial (P <0.001), midmyocardial (P=0.03), and endocardial (P <0.001) layers in AO 0 min. AO infused into the AIV immediately at Rep diffuses into the RR and reduces IS by reducing Rep injury associated with neutrophil activation.

Animals↗
PubMed2004

Uptake of 111In-Z2D3 on SPECT imaging in a swine model of coronary stent restenosis correlated with cell proliferation.

UNLABELLED: Small targets such as cell proliferation in the coronary arteries may potentially be detected with single-photon imaging using high-radiotracer-specific activity. We hypothesized that an antibody linked to polymers to increase specific radioactivity can be visualized on SPECT images and that counts in the target will correlate with the strength of the biologic signal. METHODS: Twenty-four stents were placed using the balloon overexpansion technique in the coronary arteries of 14 juvenile domestic swine. One week later, the animals received 74 MBq of (111)In-diethylenetriaminepentaacetic acid-polylysine Z2D3-F(ab')(2), and SPECT imaging was performed at 24 h. The coronary vessels were removed, and the stented vessels were processed with plastic embedding and sectioning. Medial and neointimal areas, percentage of vessel stenosis, and cell proliferation indices were quantified using a 5-bromo-2-deoxyuridine (BrdU) labeling index. Reconstructed SPECT images were interpreted for tracer uptake in coronary vessels. RESULTS: Sixteen of the vessels were positive on SPECT imaging and 10 were negative. The percentage injected dose was 0.85 +/- 0.28 x 10(-3) in scan-positive vessels and 0.34 +/- 0.11 x 10(-3) in scan-negative vessels (P < 0.001). The medial-plus-neointimal proliferative index was 42 +/- 11 in scan-positive vessels and 11 +/- 11 in scan-negative vessels (P < 0.0001). The percentage stenoses were 21% +/- 22% versus 19% +/- 15% (not statistically significant). When individual values for the stented-to-control vessel counts were plotted against BrdU labeling index, a significant relationship was found (r(2) = 0.441; P = 0.0014). CONCLUSION: These data indicate that small targets relevant to human coronary vascular disease may be detected using polymer-modified radiolabeled antibodies.

Animals↗
PubMed2003

Validation of R wave voltage endomyocardial mapping to assess myocardial fibrosis: comparison with thallium and dobutamine echocardiography in a swine model.

The first aim of this study was to validate R wave voltage values measured with a catheter-based three-dimensional mapping system (NOGA, Biosense) against myocardial fibrosis in a swine model of ameroid placement. The second aim was to correlate the UPV maps with thallium uptake and low-dose dobutamine echocardiography. The electromechanical catheter mapping system can be used to guide endomyocardial laser therapy and direct gene delivery to the myocardium. The accuracy of R wave voltage in identifying myocardial fibrosis and its comparison with other imaging technologies against histopathology has not been fully investigated in an animal model. Ameroid constrictors were placed on 24 vessels in 14 swine. Wall motion abnormalities by echocardiography were detected in distribution of the constrictors at 22 +/- 10 days. Animals underwent rest and delayed thallium imaging, low-dose dobutamine echocardiography, and R wave voltage mapping. Animals were sacrificed, hearts were removed, 4-micron slices were stained, and fibrosis was quantified. Five control animals were studied to obtain segment normalization. There was significant agreement between each imaging modality and fibrosis by chi-square analysis. The correlation for segment normalized thallium uptake and segment normalized UPV score versus fibrosis were both significant (P < 0.001) with an r2 value of 0.362 vs. thallium, and r2 = 0.445 vs. UPV. The correlation was improved using log of UPV vs. fibrosis (r = 0.532). These results help validate R wave voltage mapping as an imaging technique to identify myocardial fibrosis.

Animals↗
PubMed2002

Low event rate for stress-only perfusion imaging in patients evaluated for chest pain.

OBJECTIVES: We sought to demonstrate the safety of stress-only perfusion imaging among patients with low to medium probability of coronary disease being evaluated for chest pain. BACKGROUND: The need for performing rest in addition to stress perfusion imaging to confirm normalcy is due largely to defects created on the stress images by attenuation artifacts. A low cardiac event rate among patients undergoing stress-only imaging with attenuation correction (AC) would validate the safety of stress-only imaging. METHODS: Patients with low to medium pretest probability for coronary artery disease (CAD) referred for chest pain evaluation from July 1, 1997 to July 1, 1999, were scheduled for a two-day stress/rest tomographic (single photon emission computerized tomography, or SPECT) perfusion imaging study with Tc-99m sestamibi. Patients were imaged on a variable angle camera with AC using Gd-153 scanning line sources (Vantage ADAC, Milpitas, California). If the stress scan was normal without AC or corrected with AC, the patient did not return for rest scan and was followed. RESULTS: Seven hundred twenty-nine patients underwent stress-only imaging, and follow-up was obtained on 652 (89%) of those patients. There were 224 males and 428 females with mean age of 52 +/- 13 years. Mean follow-up was 22.3 +/- 6.4 months. The mean pretest probability was 37 +/- 24%. The non-AC images showed breast and/or diaphragmatic attenuation artifacts severe enough to have required the patient to return for rest imaging in 37% of patients, and all corrected completely with AC. During follow-up, there were two noncardiac deaths and no cardiac deaths. There was one myocardial infarction; three patients with progressive unstable angina underwent diagnostic coronary angiography showing significant CAD. The overall cardiac event rate was 0.6%. CONCLUSIONS: These results support stress-only imaging in patients with low to medium probability for CAD as a safe, time- and cost-efficient imaging modality.

Adult↗
PubMed2002

Effect of endomyocardial laser channels on regional innervation shown with (125)I-MIBG and autoradiography.

UNLABELLED: The aim of this study was to map regional innervation against regional flow early after laser channel placement using autoradiography in a porcine model. METHODS: Four juvenile male swine underwent left ventricular mapping using a catheter-based mapping system and laser treatment with 20-30 channels to the mid and distal anterior wall of the left ventricle. Three days later animals were injected with 37 MBq (125)I-metaiodobenzylguanidine (MIBG) followed in 3 h with 1,110 MBq (99m)Tc-sestamibi; 1 h later the animals were killed. Hearts were removed, perfusion fixed, and sliced into 1-cm slices. The slices best showing laser holes were selected, and circumferential sections were taken for autoradiography and hematoxylin-eosin staining. Phosphor screens were exposed for (99m)Tc and (125)I, and images were processed. The MIBG image was subtracted from the methoxyisobutylisonitrile (MIBI) image and vice versa, and color tables were applied to the difference images and overlaid on the perfusion images. Quantitative analysis of the light image data was also performed. RESULTS: Thirty-three sections from the last 3 experiments were analyzed. Acoustic damage from 30 laser channels was identified from the hematoxylin-eosin sections. Reduced MIBG relative to regional flow was seen in surrounding tissue corresponding to only 1 channel. There was no statistically significant difference in light units expressed as (MIBG - MIBI)/maximal MIBG value between laser channels and unmarked myocardial map regions. The regions identified from the color table on the map as low MIBG relative to MIBI were significantly lower than remaining laser channels and remaining myocardium. Mean light units for the regions with high MIBG relative to MIBI were significantly higher than the remaining laser channels and remaining myocardium. CONCLUSION: Using a high-resolution technique correlated with microscopic pathology in an animal model, there is negligible regional denervation 3 d after placement of endomyocardial laser channels.

3-Iodobenzylguanidine↗
PubMedDate not supplied

The prognostic value of ECG-gated SPECT imaging in patients undergoing stress Tc-99m sestamibi myocardial perfusion imaging.

BACKGROUND: The ability of stress radionuclide myocardial perfusion imaging to predict adverse cardiac events is well accepted. As left ventricular systolic function has also been shown to be an important prognostic indicator, the objective of this study was to determine whether electrocardiography (ECG)-gated single photon emission computed tomography (SPECT) functional data add additional power. METHODS AND RESULTS: In this study 3207 patients who underwent stress myocardial perfusion imaging with ECG gating, without early (</=60 days) revascularization, were studied. Subsequent nonfatal myocardial infarction and cardiac death were related to perfusion and ECG-gated SPECT ventricular function parameters. Cox proportional hazards regression analysis was used to evaluate the independent predictive value of these parameters, as well as their added utility over clinical and ECG parameters. Patients with abnormal perfusion images had an annual event rate of 5.1% compared with 1.6% for patients with normal images (P <.001). An abnormal gated SPECT wall motion score was associated with an annual event rate of 6.1% compared with 1.6% for a normal score (P <.001), and an abnormal left ventricular ejection fraction was associated with an event rate of 7.4% compared with 1.8% for normal patients (P <.001). Abnormal ECG-gated SPECT results worsened outcome in both patients with normal perfusion images and those with abnormal perfusion images. Cardiac death was predicted by the number of territories with a perfusion defect and an abnormal ejection fraction, whereas myocardial infarction was predicted by the number of territories with a perfusion defect but not by ejection fraction. CONCLUSIONS: Ventricular function data from ECG-gated SPECT add important prognostic value to data obtained from perfusion imaging alone in predicting adverse cardiac events.

Adult↗
PubMedDate not supplied

Quantitative Tc-99m sestamibi attenuation-corrected SPECT: development and multicenter trial validation of myocardial perfusion stress gender-independent normal database in an obese population.

BACKGROUND: A gender-independent stress normal database and criteria for abnormality for attenuation-corrected rest-stress technetium 99m sestamibi same-day myocardial perfusion imaging were developed by evaluation of 112 patients, validated against an obese population of 95 patients from four different clinical sites, and compared with conventional gender-matched database quantification of non-attenuation-corrected studies. METHODS AND RESULTS: These 95 validation patients (63 men) were used for prospective quantitative evaluation (mean weight, 213 +/- 57 lb; mean body mass index, 32 +/- 9 kg/m(2)). This group included 21 patients (12 men) with a lower than 5% likelihood of coronary artery disease (mean weight, 226 +/- 72 lb; mean body mass index, 34 +/- 13 kg/m(2)) and 74 who underwent cardiac catheterization within 2 months (35 with normal coronaries or coronary lesions <70%). These studies were processed twice, once by use of conventional reconstruction and gender-specific database quantification and a second time by use of attenuation correction and a single gender-independent attenuation-corrected normal database. The attenuation-corrected normal database and criteria for abnormality were developed by evaluation of 48 and 78 patients, respectively. No statistically significant differences were found when comparing attenuation-corrected perfusion distributions of normal men and women, whereas significant differences were found in the same uncorrected studies. Compared with quantitative analysis of the uncorrected studies, quantitative analysis of the attenuation-corrected studies by use of a gender-independent normal database demonstrated a significant improvement in normalcy rate (90% vs 52%, P =.006) and specificity (57% vs 29%, P =.015) in this obese population at no significant loss in sensitivity (90% vs 97%, P = not significant). CONCLUSION: Attenuation-corrected studies can be quantified with a single gender-independent normal database and a single criterion for abnormality without loss of sensitivity and with significantly better specificity and normalcy rate.

Coronary Artery Disease↗
PubMedDate not supplied

Clinical value of attenuation correction in stress-only Tc-99m sestamibi SPECT imaging.

BACKGROUND: Attenuation artifact remains a substantial limitation to confident interpretation of images and reduces laboratory efficiency by requiring comparison of stress and rest image sets. Attenuation-corrected stress-only imaging has the potential to ameliorate these limitations. METHODS AND RESULTS: Ten experienced nuclear cardiologists independently interpreted 90 stress-only electrocardiography (ECG)-gated technetium 99m sestamibi images in a sequential fashion: myocardial perfusion imaging (MPI) alone, MPI plus ECG-gated data, and attenuation-corrected MPI with ECG-gated data. Images were interpreted for diagnostic certainty (normal, probably normal, equivocal, probably abnormal, abnormal, and perceived need for rest imaging). With stress MPI data alone, only 37% of studies were interpreted as definitely normal or abnormal, with a very high perceived need for rest imaging (77%). The addition of gated data did not alter the interpretations. However, attenuation-corrected data significantly increased the number of studies characterized as definitely normal or abnormal (84%, P <.005) and significantly reduced the perceived need for rest imaging (43%, P <.005). These results were confirmed by use of a nonsequential consensus interpretation of three readers. CONCLUSION: Attenuation correction applied to studies with stress-only Tc-99m ECG-gated single photon emission computed tomography images significantly increases the ability to interpret studies as definitely normal or abnormal and reduces the need for rest imaging. These findings may improve laboratory efficiency and diagnostic accuracy.

Adult↗
PubMedDate not supplied

Value of attenuation correction on ECG-gated SPECT myocardial perfusion imaging related to body mass index.

BACKGROUND: Obesity is a growing problem in the United States, and attenuation artifacts are more prevalent in this patient group. This study evaluated the impact of attenuation correction in patients with a high body mass index (BMI). METHODS AND RESULTS: Three readers interpreted gated attenuation-corrected and non-attenuation-corrected rest/stress technetium 99m sestamibi myocardial perfusion imaging results in 116 patients (BMI <30, n = 60; BMI > or =30, n = 56) who had coronary angiography no more than 60 days after imaging. Readers were blinded to all clinical information and as to whether myocardial perfusion imaging was attenuation-corrected or non-attenuation-corrected. Sensitivity, specificity, and accuracy for detection of coronary artery disease of 70% or greater for attenuation-corrected versus non-attenuation-corrected single photon emission computed tomography (SPECT) were 86% versus 89%, 79% versus 50%, and 84% versus 79%, respectively. Sensitivity, specificity, and accuracy for attenuation-corrected versus non-attenuation-corrected SPECT for patients with BMI less than 30 were 90% versus 90%, 82% versus 64%, and 88% versus 85%, respectively. For BMI of 30 or greater, the results were 82% versus 87%, 76% versus 41%, and 80% versus 73%, respectively. There was a significant difference in specificity overall ( P = .02) and for the category of BMI of 30 or greater ( P = .03). CONCLUSIONS: This study demonstrates that electrocardiography-gated attenuation-corrected Tc-99m sestamibi SPECT myocardial perfusion imaging improves specificity compared with electrocardiography-gated non-attenuation-corrected SPECT myocardial perfusion imaging, especially in patients with BMI of 30 or greater.

Artifacts↗
PubMedDate not supplied

Sinus arrest during adenosine stress testing in liver transplant recipients with graft failure: three case reports and a review of the literature.

BACKGROUND: Nuclear stress imaging is used frequently to evaluate patients with end-stage liver disease who are being considered for orthotopic liver transplantation. METHODS AND RESULTS: We present three patients who, following graft failure, developed sinus arrest during adenosine stress testing performed in anticipation of repeat liver transplantation. All had undergone uneventful adenosine stress imaging prior to initial transplantation. The mechanisms of action, pharmacokinetics, and pharmacodynamics of adenosine are reviewed, and possible reasons for this phenomenon are discussed. Finally, cautions regarding the use of adenosine and treatment of adenosine-induced sinoatrial and atrioventricular block are reviewed. CONCLUSION: Adenosine should be used with caution in patients following orthotopic liver transplantation due to an increased risk of sinus arrest. Should sinus arrest or atrioventricular block occur, it appears to respond readily to cessation of adenosine infusion and intravenous aminophylline with no significant sequelae.

Adenosine↗