Thomas A Goldstein

Hannover Medical School, Hanover, Lower Saxony, Germany

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Publications (16)66.69 Total impact

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    ABSTRACT: OBJECTIVES: The aim of this study was to evaluate the quantitative and semiquantitative measures of regional pulmonary parenchymal perfusion in patients with chronic obstructive pulmonary disease (COPD) in relationship to global lung perfusion (GLP) and lung diffusing capacity (DLCO). MATERIALS AND METHODS: A total of 143 participants in the Multiethnic Study of Atherosclerosis COPD Study were examined by dynamic contrast-enhanced pulmonary perfusion magnetic resonance imaging (MRI) at 1.5 T. Pulmonary microvascular blood flow (PBF) was calculated on a pixel-by-pixel basis by using a dual-bolus technique and the Fermi function model. Semiquantitative parameters for regional pulmonary microvascular perfusion were calculated from signal intensity-time curves in the lung parenchyma. Intraoberserver and interobserver coefficients of variation (CVs) and correlations between quantitative and semiquantitative MRI parameters and with GLP and DLCO were determined. RESULTS: Quantitative and semiquantitative parameters of pulmonary microvascular perfusion were reproducible, with CVs for all parameters of less than 10%. Furthermore, these MRI parameters were correlated with GLP and DLCO, and there was good agreement between PBF and GLP. Quantitative and semiquantitative MRI parameters were closely correlated (eg, r = 0.86 for maximum signal increase with PBF). In participants without COPD, the physiological distribution of pulmonary perfusion could be determined by regional MRI measurements. CONCLUSION: Regional pulmonary microvascular perfusion can reliably be quantified from dynamic contrast-enhanced MRI. Magnetic resonance imaging-derived quantitative and semiquantitative perfusion measures correlate with GLP and DLCO.
    Investigative radiology 02/2013; · 4.85 Impact Factor
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    ABSTRACT: PURPOSE To compare quantitative and semiquantitative measures of regional pulmonary parenchymal perfusion using dynamic contrast-enhanced MRI and to correlate these regional lung perfusion measures with global lung perfusion (GLP) and lung diffusing capacity (DLCO). METHOD AND MATERIALS One hundred and forty participants in the MESA COPD study (n=81 COPD; n=59 controls) were included in the analysis. Pulmonary perfusion was measured on a 1.5 T MRI scanner (GE Healthcare) using time resolved imaging of contrast kinetics (TRICKS) with 0.1 mmol/kg Gd-DTPA injected at 5 ml/s. The arterial input function for absolute quantification of pulmonary blood flow (PBF) was derived from cardiac perfusion MRI in the right-ventricular cavity (0.05 mmol/kg Gd-DTPA). PBF was calculated on a pixel-by-pixel basis by using the Fermi function model and displayed in parameter maps. Semiquantitative parameters for regional lung perfusion were determined from signal-intensity time curves: peak signal increase (SI) = peak - 20% signal intensities; upslope = maximum rate of signal increase as determined by use of a linear fit. Mean perfusion values over 3 coronal slices and both lungs were calculated. GLP was calculated as the ratio of cardiac output and total lung volume. RESULTS Overall, mean total regional PBF (84±45 ml*min-1*100ml-1) was in excellent agreement with GLP (86±21 ml*min-1*100ml-1) and was positively correlated with GLP (r=0.45, p<0.001) and DLCO (r=0.31, p=0.007). In participants without COPD and emphysema <5% (n=59), regional PBF was significantly higher in the posterior (dependent) lung (141±64 ml*min-1*100ml-1) compared to the anterior (non-dependent) lung (86±43 ml*min-1*100ml-1, p<0.001). Quantitative parameters significantly correlated with semiquantitative parameters of regional perfusion: Mean total PBF significantly correlated with SI (r=0.82, p<0.001) and upslope (r=0.73, p<0.001). Intra- and interobserver coefficients of variations for quantitative and semiquantitative measures were <10%. CONCLUSION Regional pulmonary PBF can reliably be quantified from dynamic contrast-enhanced MRI. Due to close correlation with semiquantitative parameters, SI and upslope may be used as surrogate markers for regional pulmonary PBF. CLINICAL RELEVANCE/APPLICATION Non-invasive quantification of regional pulmonary tissue perfusion using MRI may help to understand the relevance of regional perfusion abnormalities in lung diseases.
    Radiological Society of North America 2012 Scientific Assembly and Annual Meeting; 11/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
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    Journal of Cardiovascular Magnetic Resonance 02/2012; 14 Suppl 1:P158. · 4.44 Impact Factor
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    ABSTRACT: To quantify resting myocardial blood flow (MBF) in the left ventricular (LV) wall of HCM patients and to determine the relationship to important parameters of disease: LV wall thickness, late gadolinium enhancement (LGE), T2-signal abnormalities (dark and bright signal), LV outflow tract obstruction and age. Seventy patients with proven HCM underwent cardiac MRI. Absolute and relative resting MBF were calculated from cardiac perfusion MRI by using the Fermi function model. The relationship between relative MBF and LV wall thickness, T2-signal abnormalities (T2 dark and T2 bright signal), LGE, age and LV outflow gradient as determined by echocardiography was determined using simple and multiple linear regression analysis. Categories of reduced and elevated perfusion in relation to non- or mildly affected reference segments were defined, and T2-signal characteristics and extent as well as pattern of LGE were examined. Statistical testing included linear and logistic regression analysis, unpaired t-test, odds ratios, and Fisher's exact test. 804 segments in 70 patients were included in the analysis. In a simple linear regression model LV wall thickness (p<0.001), extent of LGE (p<0.001), presence of edema, defined as focal T2 bright signal (p<0.001), T2 dark signal (p<0.001) and age (p = 0.032) correlated inversely with relative resting MBF. The LV outflow gradient did not show any effect on resting perfusion (p = 0.901). Multiple linear regression analysis revealed that LGE (p<0.001), edema (p = 0.026) and T2 dark signal (p = 0.019) were independent predictors of relative resting MBF. Segments with reduced resting perfusion demonstrated different LGE patterns compared to segments with elevated resting perfusion. In HCM resting MBF is significantly reduced depending on LV wall thickness, extent of LGE, focal T2 signal abnormalities and age. Furthermore, different patterns of perfusion in HCM patients have been defined, which may represent different stages of disease.
    PLoS ONE 01/2012; 7(7):e41974. · 3.53 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2011; · 4.44 Impact Factor
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    ABSTRACT: To evaluate the relationships of right ventricular (RV) and left ventricular (LV) myocardial perfusion reserves with ventricular function and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) by using adenosine stress perfusion cardiac magnetic resonance (MR) imaging. This HIPAA-compliant study was institutional review board approved. Twenty-five patients known or suspected to have PAH underwent right heart catheterization and adenosine stress MR imaging on the same day. Sixteen matched healthy control subjects underwent cardiac MR imaging only. RV and LV perfusion values at rest and at adenosine-induced stress were calculated by using the Fermi function model. The MR imaging-derived RV and LV functional data were calculated by using dedicated software. Statistical testing included Kruskal-Wallis tests for continuous data, Spearman rank correlation tests, and multiple linear regression analyses. Seventeen of the 25 patients had PAH: 11 with scleroderma-associated PAH, and six with idiopathic PAH. The remaining eight patients had scleroderma without PAH. The myocardial perfusion reserve indexes (MPRIs) in the PAH group (median RV MPRI, 1.7 [25th-75th percentile range, 1.3-2.0]; median LV MPRI, 1.8 [25th-75th percentile range, 1.6-2.1]) were significantly lower than those in the scleroderma non-PAH (median RV MPRI, 2.5 [25th-75th percentile range, 1.8-3.9] [P = .03]; median LV MPRI, 4.1 [25th-75th percentile range, 2.6-4.8] [P = .0003]) and control (median RV MPRI, 2.9 [25th-75th percentile range, 2.6-3.6] [P < .01]; median LV MPRI, 3.6 [25th-75th percentile range, 2.7-4.1] [P < .01]) groups. There were significant correlations between biventricular MPRI and both mean pulmonary arterial pressure (mPAP) (RV MPRI: ρ = -0.59, Bonferroni P = .036; LV MPRI: ρ = -0.79, Bonferroni P < .002) and RV stroke work index (RV MPRI: ρ = -0.63, Bonferroni P = .01; LV MPRI: ρ = -0.75, Bonferroni P < .002). In linear regression analysis, mPAP and RV ejection fraction were independent predictors of RV MPRI. mPAP was an independent predictor of LV MPRI. Biventricular vasoreactivity is significantly reduced with PAH and inversely correlated with RV workload and ejection fraction, suggesting that reduced myocardial perfusion reserve may contribute to RV dysfunction in patients with PAH.
    Radiology 10/2010; 258(1):119-27. · 6.34 Impact Factor
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    ABSTRACT: Myocardial oxygen extraction fraction (OEF) during hyperemia can be estimated using a double-inversion-recovery-prepared T(2)-weighted black-blood sequence. Severe irregular electrocardiogram (ECG) triggering due to elevated heart rate and/or arrhythmias may render it difficult to adequately suppress the flowing left ventricle blood signal and thus potentially cause errors in the estimates of myocardial OEF. Thus, the goal of this study was to evaluate another black-blood technique, a diffusion-weighted-prepared turbo spin echo sequence for its ability to determine regional myocardial OEF during hyperemia. Control dogs and dogs with acute coronary artery stenosis were imaged with both the double-inversion-recovery- and diffusion-weighted-prepared turbo spin echo sequences at rest and during either dipyridamole or dobutamine hyperemia. Validation of MRI OEF estimates was performed using blood sampling from the artery and coronary sinus in control dogs. The two methods showed comparable correlations with blood sampling results (R(2) = 0.9). Similar OEF estimations for all dogs were observed, except for the group of dogs with severe coronary stenosis during dobutamine stress. In these dogs, the diffusion-weighted method provided more physiologically reasonable OEF (hyperemic OEF = 0.75 +/- 0.08 versus resting OEF of 0.6) than the double-inversion-recovery method (hyperemic OEF = 0.56 +/- 0.10). Diffusion-weighted preparation may be a valuable alternative for more accurate oxygenation measurements during irregular ECG-triggering.
    Magnetic Resonance in Medicine 06/2010; 63(6):1675-82. · 3.27 Impact Factor
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    ABSTRACT: To validate fast perfusion mapping techniques in a setting of coronary artery stenosis, and to further assess the relationship of absolute myocardial blood volume (MBV) and blood flow (MBF) to global myocardial oxygen demand. A group of 27 mongrel dogs were divided into 10 controls and 17 with acute coronary stenosis. On 1.5-T MRI, first-pass perfusion imaging with a bolus injection of a blood-pool contrast agent was performed to determine myocardial perfusion both at rest and during either dipyridamole-induced vasodilation or dobutamine-induced stress. Regional values of MBF and MBV were quantified by using a fast mapping technique. Color microspheres and (99m)Tc-labeled red blood cells were injected to obtain respective gold standards. Microsphere-measured MBF and (99m)Tc-measured MBV reference values correlated well with the MR results. Given the same changes in MBF, changes in MBV are twofold greater with dobutamine than with dipyridamole. Under dobutamine stress, MBV shows better association with total myocardial oxygen demand than MBF. Coronary stenosis progressively reduced this association in the presence of increased stenosis severity. MR first-pass perfusion can rapidly estimate regional MBF and MBV. Absolute quantification of MBV may add additional information on stenosis severity and myocardial viability compared with standard qualitative clinical evaluations of myocardial perfusion.
    European Radiology 02/2010; 20(8):2005-12. · 4.34 Impact Factor
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    ABSTRACT: Understanding the oxygen consumption of the left ventricular myocardium provides important insight into the relationship between myocardial oxygen supply and demand. In other territories, cardiac magnetic resonance has been utilized to measure myocardial oxygen consumption with a blood level oxygen dependent (BOLD) technique. The BOLD technology requires repetitive sampling of stationary tissues and is frequently implemented in areas such as the brain. A limitation to utilizing BOLD cardiac magnetic resonance techniques in the heart has been cardiac motion. In this study, we document a methodology for acquiring BOLD images in the heart and demonstrate the utility of the technique for identifying associations between myocardial oxygen consumption and blood flow.
    JACC. Cardiovascular imaging 11/2009; 2(11):1313-20. · 14.29 Impact Factor
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    ABSTRACT: A comprehensive evaluation of myocardial ischemia requires measures of both oxygen supply and demand. Positron emission tomography (PET) is currently the gold standard for such evaluations, but its use is limited because of its ionizing radiation, limited availability, and high cost. A cardiac MRI method was developed for assessing myocardial oxygenation. The purpose of this study was to evaluate and validate this technique compared with PET during pharmacological stress in a canine model of coronary artery stenosis. Twenty-one beagles and small mongrel dogs without coronary artery stenosis (controls) or with moderate to severe acute coronary artery stenosis underwent MRI and PET imaging at rest and during dipyridamole vasodilation or dobutamine stress to induce a wide range of changes in cardiac perfusion and oxygenation. MRI first-pass perfusion imaging was performed to quantify myocardial blood flow and volume. The MRI blood oxygen level-dependent technique was used to determine the myocardial oxygen extraction fraction during pharmacological hyperemia. Myocardial oxygen consumption was determined by the Fick law. In the same dogs, (15)O-water and (11)C-acetate were used to measure myocardial blood flow and myocardial oxygen consumption, respectively, by PET. Regional assessments were performed for both MR and PET. MRI data correlated nicely with PET values for myocardial blood flow (R(2)=0.79, P<0.001), myocardial oxygen consumption (R(2)=0.74, P<0.001), and oxygen extraction fraction (R(2)=0.66, P<0.01). Cardiac MRI methods may provide an alternative to radionuclide imaging in settings of myocardial ischemia. Our newly developed quantitative MRI oxygenation imaging technique may be a valuable noninvasive tool to directly evaluate myocardial energetics and efficiency.
    Circulation Cardiovascular Imaging 11/2009; 3(1):41-6. · 5.80 Impact Factor
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    ABSTRACT: Accurate and fast quantification of myocardial blood flow (MBF) with MR first-pass perfusion imaging techniques on a pixel-by-pixel basis remains difficult due to relatively long calculation times and noise-sensitive algorithms. In this study, Zierler's central volume principle was used to develop an algorithm for the calculation of MBF with few assumptions on the shapes of residue curves. Simulation was performed to evaluate the accuracy of this algorithm in the determination of MBF. To examine our algorithm in vivo, studies were performed in nine normal dogs. Two first-pass perfusion imaging sessions were performed with the administration of the intravascular contrast agent Gadomer at rest and during dipyridamole-induced vasodilation. Radiolabeled microspheres were injected to measure MBF at the same time. MBF measurements in dogs using MR methods correlated well with the microsphere measurements (R2=0.96, slope=0.9), demonstrating a fair accuracy in the perfusion measurements at rest and during the vasodilation stress. In addition to its accuracy, this method can also be optimized to run relatively fast, providing potential for fast and accurate myocardial perfusion mapping in a clinical setting.
    Magnetic Resonance in Medicine 07/2008; 59(6):1394-400. · 3.27 Impact Factor
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    Kyle McCommis, Thomas Goldstein, Robert Gropler, Jie Zheng
    Journal of Cardiovascular Magnetic Resonance 01/2008; · 4.44 Impact Factor
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    ABSTRACT: Myocardial blood volume (MBV) may provide complementary information about myocardial oxygen needs and viability. The aim of this study is to examine a Cardiovascular Magnetic Resonance (CMR) perfusion method to quantify the changes in MBV, in comparison with the radiolabeled 99mTc-Red-Blood-Cell (RBC) method. Normal mongrel dogs (n=12) were used in this study. Eight dogs were injected intravenously with dipyridamole, and 4 dogs were given dobutamine during the MR scans. CMR first-pass perfusion imaging was performed at rest and during the pharmacological stress. An intravascular contrast agent, Gadomer (Schering AG, Berlin, Germany), was injected (0.015 mmol/kg) as a bolus during the scans. A perfusion quantification method was applied to obtain MBV maps. Radiolabeled-RBCs were injected at the end of the study to measure reference MBV at rest (n=4), during dipyridamole vasodilation (n=4), and during dobutamine stress (n=4). Myocardial blood flow (MBF) increased approximately 3-fold with both dipyridamole and dobutamine injections. Transmural MBV values measured by CMR were closely correlated with those measured by 99mTc method (CMR:MBV=6.2+/-1.3, 7.2+/-0.8, and 8.3+/-0.5 mL/100 g, at rest, with dipyridamole, and with dobutamine, respectively. 99mTc-RBC: MBV=6.1+/-0.5, 7.0+/-0.9, and 8.6+/-0.7 mL/100 g). Dobutamine stress significantly increased MBV by CMR (33%) and 99mTc methods (35%). During dipyridamole induced vasodilation, MBV increased non-significantly by 14% with the 99mTc method and 1% with CMR method, which agreed well with other reports. First-pass perfusion CMR with the injection of intravascular contrast agents is a promising non-invasive approach for the assessment of MBV both at rest and pharmacologically induced stress.
    Journal of Cardiovascular Magnetic Resonance 02/2007; 9(5):785-92. · 4.44 Impact Factor
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    ABSTRACT: Mapping of myocardial blood flow (MBF) with first-pass perfusion imaging is becoming an important tool in the study of coronary artery disease. In this study a wavelet-based denoising method was developed to improve the accuracy of pixel-by-pixel MBF maps. We performed an in vivo study in five stenotic dogs with 70% stenosis in the left coronary arteries. First-pass perfusion imaging sessions were performed by administering the intravascular contrast agent Gadomer at rest and during dipyridamole-induced vasodilation. Color microspheres (MS) were injected into the dogs to measure MBF at the same time. After denoising was performed, the signal-to-noise ratio (SNR) of the first-pass perfusion image improved by approximately 180%, whereas spatial variation of MBF maps decreased 38%. It was also found that the correlation of MBFs measured by MRI with the MS method indicates a significant improvement with the denoising method (R2 increased from 0.24 to 0.78, P < .001). This suggests that the wavelet denoising method may be an effective way to increase the accuracy of pixel-by-pixel MBF quantification and reduce spatial variation, and may be applicable to other forms of noise-sensitive image analysis.
    Magnetic Resonance in Medicine 09/2006; 56(2):439-45. · 3.27 Impact Factor
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    ABSTRACT: Purpose Historically, assessments of myocardial perfusion have relied heavily on measurements of myocardial blood flow (MBF). However, because only ~50% of capillaries are functional at rest [1], the recruitment of capillaries, or changes in myocardial blood volume (MBV), may also play a significant role in supplying O 2 to the myocardium [2]. Our MRI methods can quantify MBF, MBV, oxygen extraction fraction (OEF), and estimate oxygen consumption (MVO 2) with Fick's law: MVO 2 ∝ OEF x MBF. In this ongoing study, we are imaging beagles with MRI and PET to determine the accuracy of MRI methods. Methods So far, eight beagle dogs were used in this ongoing study, divided into 4 groups (Table). Stenosis was created by using an MR-compatible, adjustable clamp in the proximal left anterior descending coronary artery (LAD). MR imaging was performed on a 1.5T Sonata scanner (Siemens Medical Solutions, Erlanger, Germany). MR first-pass perfusion scans using a turboFLASH sequence were performed at rest and during hyperemia. 0.015 mmol/kg Gadomer (Bayer Schering Pharma AG, Berlin, Germany), an intravascular contrast agent, was injected as a bolus. A validated perfusion quantification method designed in our lab [3], was applied to obtain MBF and MBV maps (Figure 1). OEF during hyperemia was determined by a two compartment model with myocardial T 2 that was measured with a 2-D segmented black blood turbo spin-echo (TSE) sequence [4]. Rest OEF was assumed to be 0.6, which is based on values measured in normal dogs using AV blood sampling at rest [5]. PET imaging was performed on a Focus 220 MicroPET scanner (Concorde Medical Systems, Knoxville, TN). MBF was determined with 15 O-water (avg. 7.59 mCi), and MVO 2 was measured with 11 C-acetate (avg. 8.39 mCi). OEF was then determined with Fick's law. Data from both LAD-perfused anterior and left circumflex (LCx)-perfused inferior myocardial beds was determined. Results As expected, dipyridamole and dobutamine both produced large increases in MBF (47.4 ± 16.4% and 55.6 ± 16.7%, respectively) in normal myocardial regions. Both agents also produced significant increases in MBV (17.9 ± 11.4% for dipyridamole, 32.8 ± 12.8% for dobutamine), as well as in MVO 2 (15.7 ± 9.9% for dipyridamole and 43.6 ± 18.4% for dobutamine) in normal myocardium. The considerably larger increases with dobutamine are due to the combination of inotropic and chronotropic stimulation. Thus far, our PET results show good agreement with our MR measurements (MBF R 2 = 0.796, OEF R 2 = 0.629, MVO 2 R 2 = 0.664) (Figure 2). Once more subjects are completed; these correlations are expected to become more significant.

Publication Stats

94 Citations
66.69 Total Impact Points


  • 2012
    • Hannover Medical School
      • Institute for Biometry
      Hanover, Lower Saxony, Germany
    • Johns Hopkins University
      • Division of Cardiology
      Baltimore, Maryland, United States
    • University of California, Los Angeles
      • Department of Mathematics
      Los Angeles, California, United States
  • 2011–2012
    • Stanford University
      Palo Alto, California, United States
  • 2006–2010
    • Washington University in St. Louis
      San Luis, Missouri, United States
  • 2009
    • Bayer HealthCare
      Leverkusen, North Rhine-Westphalia, Germany