Sven Michael Spira

Assessment of tumor vascularity in lung cancer using volume perfusion CT (VPCT) with histopathologic comparison: a further step toward an individualized tumor characterization.

Objective To measure perfusion in different lung cancer subtypes and compare results with histopathological/immunohistochemical results. Methods Seventy-two consecutive untreated patients with lung cancer (40 adenocarcinomas, 20 squamous cell, and 12 small cell lung cancers) were enrolled. A 40-second volume perfusion computed tomography of the tumor bulk was obtained. Blood flow (BF), blood volume (BV), and transit constant were determined. Tumor volume and tumor necrosis were determined on contrast-enhanced computed tomography. Pathologic specimens were assessed for microvessel density (MVD), hypoxia-induced transcription (hif-1/-2), and proliferation (Ki-67). Results Higher MVD is associated with higher BF and BV. Higher tumor grade leads to lower BF but increased necrosis and tumor volume. Markers of hypoxia were independent from perfusion parameters, extent of necrosis or MVD. Blood flow, BV, and MVD were not significantly different among lung cancer subtypes. Transit constant was significantly reduced in small cell lung cancer versus adenocarcinoma. Conclusions Perfusion values are related to MVD and tumor grade but vary considerably among lung cancer subtypes.

Subjective Life Horizon and Portfolio Choice

Using data from a U.S. household survey, we examine the empirical relation between subjective life horizon (i.e., the self-reported expectation of remaining life span) and portfolio choice. We find that equity portfolio shares are higher for investors with longer horizons, controlling for gender-specific age effects, socio-economic characteristics, health, and optimism. Our result is robust to accounting for the endogeneity of equity market participation or instrumenting subjective life horizon with parental survival. Finally, we show that the effect of a shortening horizon on portfolio allocation is stronger for households without bequest motives.

Effect of Scan Time on Perfusion and Flow Extraction Product (K-Trans) Measurements in Lung Cancer Using Low-Dose Volume Perfusion CT (VPCT)

RATIONALE AND OBJECTIVES To assess the effect of measurement time on blood flow (BF), blood volume (BV), and k-trans-values (flow extraction product) in patients undergoing volume perfusion computed tomography (VPCT) for lung cancer. MATERIALS AND METHODS This prospective study was approved by our local Research Ethics Committee and informed consent was obtained in all patients. Between December 2009 and December 2010, 75 VPCT scans were obtained in 54 consecutive patients (15 women, 39 men) with histologically confirmed lung cancer. A 64-second VPCT of the tumor (80 kV, 60 mAs) using 128 × 0.6-mm collimation, 6.9-cm z-axis coverage and a total of 26 volume measurements, was performed. BF, BV, and K(trans) were determined. Data evaluation was performed for different measurement times (64 seconds, 45 seconds, 39 seconds, and 36 seconds) by removing the last two, four, and five scans and repeating the analysis. A one-way repeated-measures analysis of variance was used to test for effects of measurement time on BF, BV, and k-trans and unpaired/paired Student t-tests were applied for comparisons within/between groups, respectively. RESULTS No effect of measurement time on BF values was noted (P > .05), whereas a significant decrease of BV values (at 39 seconds: 71% ± 2% of 64-second values) and a significant increase of k-trans-values (at 39 seconds: 146% ± 8% of 64-second values) were observed with progressively shortened measurement time (P < .05, respectively). Additionally, with reduced measurement time, the increase in k-trans-values was significantly more pronounced in those patient groups with higher BV (at 39 seconds: 171% ± 15% versus 120% ± 3% of 64-second measurements), and those with lower k-trans (at 39 seconds: 167% ± 16% versus 126% ± 4% of 64-second measurements) (P < .05, respectively). CONCLUSION Whereas estimation of BF in lung cancer was independent from VPCT measurement time within the chosen ranges, approximation of both BV and k-trans was affected by measurement duration. A fixed measurement time of 40 seconds is recommended.

Perfusion and Flow Extraction Product as Potential Discriminators in Untreated Follicular and Diffuse Large B Cell Lymphomas Using Volume Perfusion CT With Attempt at Histopathologic Explanation

OBJECTIVE The purpose of this article is to measure perfusion parameters, including transit constant (K(trans)), in untreated follicular and diffuse large B cell lymphoma using volume perfusion CT, to establish their discriminating role and to search for a possible histopathologic background. SUBJECTS AND METHODS Between January 2010 and June 2011, 46 consecutive patients with untreated histologically confirmed follicular lymphoma (n = 16) or diffuse large B cell lymphoma (n = 30) were enrolled. A 40-second volume perfusion CT of the tumor bulk using 6.9-cm z-axis coverage and a total of 26 volume measurements was performed. Blood flow (BF), blood volume (BV), and K(trans) were determined. Tumor size was recorded as the product of long- and short-axis diameters. In 13 of 46 patients, pathologic specimens of an appropriate size were available for assessment of microvessel density (MVD) and microvascular luminal diameter for comparison with volume perfusion CT measurements. RESULTS Mean BF, BV, and K(trans) values were significantly higher in follicular lymphoma than in diffuse large B cell lymphoma, even after controlling for patient age and tumor size (p < 0.05, respectively). Although MVD was slightly, but not significantly, higher in follicular lymphoma versus diffuse large B cell lymphoma (p > 0.05), microvascular luminal diameter was significantly larger in follicular lymphoma than in diffuse large B cell lymphoma (p < 0.05). We defined cutoff values for BF, BV, and K(trans). If the cutoff points are met for all three parameters, the overall accuracy for correctly identifying diffuse large B cell lymphoma and follicular lymphoma was 90.5% and 87.5%, respectively. CONCLUSION Volume perfusion CT allows assessment of differences in vascularity of follicular and diffuse large B cell lymphomas, reflecting vascular luminal variability and histopathologic anatomy.

Midtreatment evaluation of lymphoma response to chemotherapy by volume perfusion computed tomography.

Objective The aim of this study was to search for chemotherapy-induced perfusion changes of diffuse large B-cell lymphoma, follicular lymphoma, and Hodgkin lymphoma at midtreatment versus baseline volume perfusion computed tomography (VPCT). Methods Forty-five consecutive patients with untreated diffuse large B-cell lymphoma, follicular lymphoma, and Hodgkin lymphoma received VPCT examinations of the tumor bulk at baseline and during chemotherapy (midtreatment). Blood flow (BF), blood volume (BV), and transit constant (K-trans) were determined. Treatment response was categorized according to the Cheson criteria into complete or partial remission and stable or relapsed/progressive disease. Results Midtreatment follow-up showed a reduction in BF, BV, and K-trans in all lymphoma subtypes compared with baseline. The reduction in BV was less pronounced in larger tumors. Notably, BF, BV, and K-trans decreased in the responders (complete remission/partial remission) when compared with the nonresponders (stable or relapsed/progressive disease). Less than 10% reduction in BF was shown to be the best VPCT criterion for the identification of nonresponse. Conclusions Chemotherapy-induced perfusion changes in responders are recognizable at midtreatment VPCT.

Does volume perfusion computed tomography enable differentiation of metastatic and non-metastatic mediastinal lymph nodes in lung cancer patients? A feasibility study.

Abstract Objectives: To compare the perfusion characteristics of mediastinal lymph node metastases with those of non-metastatic nodes in patients with newly diagnosed lung cancer using volume perfusion computed tomography (VPCT). Materials and methods: Between January 2010 and October 2011, 101 patients with histologically confirmed, untreated lung cancer received a 40-s VPCT of the tumor bulk; 32/101 patients had evident hilar/mediastinal metastatic disease and 17/101 patients had proven non-metastasized lymph nodes within the VPCT scan range. Validation or exclusion of metastatic node involvement was proven by mediastinoscopy, biopsy, positron emission tomography imaging and/or unequivocal volume dynamics on follow-up computed tomography. A total of 45 metastases and 23 non-metastatic lymph nodes were found within the scan range and subsequently evaluated. Blood flow (BF), blood volume (BV) and Ktrans were determined. Tumor volume was recorded as whole tumor volume. Results: In a comparison between metastatic and non-metastatic lymph nodes, we controlled for age, lymph node volume, lung tumor volume, lung tumor location, and histologic type effects and found no significant differences with respect to BF, BV, Ktrans or heterogeneity in nodal perfusion (P > 0.05, respectively), even after adjusting lymph node perfusion values to the perfusion parameters of the primary tumor (P > 0.05, respectively). Metastatic lymph node volume had a significant increasing effect on perfusion heterogeneity (P < 0.05, respectively) and BV in the primary was a highly significant factor for BV in metastatic disease (P < 0.001). Conclusion: Perfusion characteristics of mediastinal metastatic and non-metastatic lymph nodes in untreated lung cancer show considerable overlap, so that a reliable differentiation via VPCT is not possible.

Volume and attenuation computed tomography measurements for interim evaluation of Hodgkin and follicular lymphoma as an additional surrogate parameter for more confident response monitoring: a pilot study.

Abstract Purpose: To retrospectively determine the potential role of additional computed tomography (CT) attenuation measurements for interim response evaluation in residual masses of patients with Hodgkin disease (HD) and follicular non-Hodgkin lymphoma (NHL). Materials and methods: In this retrospective study, 39 patients with HD and 35 patients with NHL presented with residual masses at mid-treatment CT (after 2–4 cycles of chemotherapy) and were assessed via contrast-enhanced CT at baseline, mid-treatment and post-treatment. Volume was recorded as whole-tumour volume. A tumour attenuation ratio (TAR) was calculated as the quotient of attenuation between tumour and muscle at the respective point in time versus baseline. The standard deviation of attenuation values within the tumour volume was recorded to estimate tumour heterogeneity. Results were correlated with relapse-free survival determined at a minimum of 12 months after end-treatment CT. Results: Tumour volume and TAR at interim versus baseline control were significantly reduced in responders compared with non-responders, even after controlling for age, stage, treatment regimen, and baseline tumour volume. No significant differences with respect to the standard deviation of attenuation values within the tumour volumes (tumour heterogeneity) were observed. The volume and attenuation CT (VACT) criteria yielded the highest sensitivities and specificities for the identification of non-response at a threshold of a >20% increase in volume and an increase in TAR at interim control, i.e. 88% (NHL 80%, HD 100%) and 98% (NHL 97%, HD 100%), respectively. The negative predictive values reached by VACT analysis were ≥97%, according to both parameters. Conclusion: Mid-treatment response assessment of residual masses in patients with HD and NHL using VACT may aid in the risk stratification as an additional surrogate parameter.