Publications by authors named "Ulrike Haberland"

20 Publications

  • Page 1 of 1

Feasibility of intraprocedural integration of cardiac CT to guide left ventricular lead implantation for CRT upgrades.

J Cardiovasc Electrophysiol 2021 Mar 10;32(3):802-812. Epub 2021 Feb 10.

Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Background: Optimal positioning of the left ventricular (LV) lead is an important determinant of cardiac resynchronization therapy (CRT) response.

Objective: Evaluate the feasibility of intraprocedural integration of cardiac computed tomography (CT) to guide LV lead implantation for CRT upgrades.

Methods: Patients undergoing LV lead upgrade underwent ECG-gated cardiac CT dyssynchrony and LV scar assessment. Target American Heart Association segment selection was determined using latest non-scarred mechanically activating segments overlaid onto real-time fluoroscopy with image co-registration to guide optimal LV lead implantation. Hemodynamic validation was performed using a pressure wire in the LV cavity (dP/dt ).

Results: 18 patients (male 94%, 55.6% ischemic cardiomyopathy) with RV pacing burden 60.0 ± 43.7% and mean QRS duration 154 ± 30 ms underwent cardiac CT. 10/10 ischemic patients had CT evidence of scar and these segments were excluded as targets. Seventeen out of 18 (94%) patients underwent successful LV lead implantation with delivery to the CT target segment in 15 out of 18 (83%) of patients. Acute hemodynamic response (dP/dt  ≥ 10%) was superior with LV stimulation in CT target versus nontarget segments (83.3% vs. 25.0%; p = .012). Reverse remodeling at 6 months (LV end-systolic volume improvement ≥15%) occurred in 60% of subjects (4/8 [50.0%] ischemic cardiomyopathy vs. 5/7 [71.4%] nonischemic cardiomyopathy, p = .608).

Conclusion: Intraprocedural integration of cardiac CT to guide optimal LV lead placement is feasible with superior hemodynamics when pacing in CT target segments and favorable volumetric response rates, despite a high proportion of patients with ischemic cardiomyopathy. Multicentre, randomized controlled studies are needed to evaluate whether intraprocedural integration of cardiac CT is superior to standard care.
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March 2021

Combined computed tomographic perfusion and mechanics with predicted activation pattern can successfully guide implantation of a wireless endocardial pacing system.

Europace 2020 02;22(2):298

School of Biomedical Engineering and Imaging Sciences, King's College London, 4th Floor, North Wing, St Thomas' Hospital, London, SE1 7EH, UK.

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February 2020

Dose Optimization of Perfusion-derived Response Assessment in Hepatocellular Carcinoma Treated with Transarterial Chemoembolization: Comparison of Volume Perfusion CT and Iodine Concentration.

Acad Radiol 2019 09 25;26(9):1154-1163. Epub 2018 Oct 25.

Eberhard Karls University, University Hospital Tübingen, Department of Radiology, Diagnostic and Interventional Radiology, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany; University Hospital Basel, University of Basel, Department of Radiology, Petersgraben 4, CH-4031 Basel, Switzerland. Electronic address:

Rationale And Objectives: We assessed the value of iodine concentration (IC) as a perfusion-derived response marker for hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) in comparison with volume perfusion computed tomography (VPCT) parameters.

Materials And Methods: Forty-one HCC lesions in 32 patients examined before and after TACE were analyzed retrospectively. VPCT-parameters were calculated and lesion iodine-maps were computed using subtraction of the baseline and the scan 7 seconds after aortic peak enhancement from the corresponding 80 kVp-VPCT data set. Modified RECIST was used as standard response criteria. Comparisons were performed using Student's t test for normal distributed data and Mann-Whitney U test for non-normal distributed data. Additionally, correlation analysis, receiver operating characteristics (ROC) and interreader agreement were assessed.

Results: In responding lesions, mean pre-TACE IC and blood flow (BF) were 131.2 mg/100 mL and 96.7 mL/100 mL/min, decreasing to IC 25.6 mg/100 mL (P < 0.001) and BF 28.5 mL/100 mL/min (P < 0.001) post-TACE. In nonresponding lesions, the values remained almost unchanged: pre-TACE: mean BF 79.3 mL/100 mL/min and mean IC 90.4 mg/100 mL; post-TACE: mean BF 71.3 mL/100 mL/min (n.s.) and mean IC 105.4 mg/100 mL (n.s.). Differences in IC-values revealed a high sensitivity/specificity of 96.7%/81.8%. IC and VPCT-parameters showed strong, positive correlations. Mean volume CT dose index for VPCT was 63.4 mGy and 4.9 mGy for iodine maps.

Conclusion: Thus, IC is a meaningful perfusion marker for local therapy response monitoring in HCC that can be acquired with low radiation dose. This information is important for further therapy response applications using dual and single energy CT.
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September 2019

Dual-energy CT for liver iron quantification in patients with haematological disorders.

Eur Radiol 2019 Jun 7;29(6):2868-2877. Epub 2018 Nov 7.

Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076, Tuebingen, Germany.

Objectives: To retrospectively quantify liver iron content in haematological patients suspected of transfusional haemosiderosis using dual-energy CT (DECT) and correlate with serum ferritin levels and estimated quantity of transfused iron.

Methods: One hundred forty-seven consecutive dual-source dual-energy non-contrast chest-CTs in 110 haematologic patients intended primarily for exclusion of pulmonary infection between September 2016 and June 2017 were retrospectively evaluated. Image data was post-processed with a software prototype. After material decomposition, an iron enhancement map was created and freehand ROIs were drawn including most of the partially examined liver. The virtual iron content (VIC) was calculated and expressed in milligram/millilitre. VIC was correlated with serum ferritin and estimated amount of transfused iron. Scans of patients who had not received blood products were considered controls.

Results: Forty-eight (32.7%) cases (controls) had not received any blood transfusions whereas 67.3% had received one transfusion or more. Median serum ferritin and VIC were 138.0 μg/dl (range, 6.0-2628.0 μg/dl) and 1.33 mg/ml (range, - 0.94-7.56 mg/ml) in the post-transfusional group and 27.0 μg/dl (range, 1.0-248.0 μg/dl) and 0.61 mg/ml (range, - 2.1-2.4) in the control group. Correlation between serum ferritin and VIC was strong (r = 0.623; p < 0.001) as well as that between serum ferritin and estimated quantity of transfused iron (r = 0.681; p < 0.001).

Conclusions: Hepatic VIC obtained via dual-energy chest-CT examinational protocol strongly correlates with serum ferritin levels and estimated amount of transfused iron and could therefore be used in the routine diagnosis for complementary evaluation of transfusional haemosiderosis.

Key Points: • Virtual liver iron content was measured in routine chest-CTs of haematological patients suspected of having iron overload. Chest-CTs were primarily intended for exclusion of pulmonary infection. • Measurements correlate strongly with the most widely used blood marker of iron overload serum ferritin (after exclusion of infection) and the amount of transfused iron. • Liver VIC could be used for supplemental evaluation of transfusional haemosiderosis in haematological patients.
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June 2019

Diagnostic performance of different perfusion algorithms for the detection of angiographical spasm.

J Neuroradiol 2018 Sep 2;45(5):290-294. Epub 2018 Feb 2.

Department of Diagnostic and Interventional Neuroradiology, RWTH Aachen University, 52074 Aachen, Germany; Siemens Healthcare GmbH, 91052 Forchheim, Germany. Electronic address:

Purpose: To assess the diagnostic utility of different perfusion algorithms for the detection of angiographical terial spasm.

Method: During a 2-year period, 45 datasets from 29 patients (54.2±10,75y, 20F) with suspected cerebral vasospasm after aneurysmal subarachnoid hemorrhage were included. Volume Perfusion CT (VPCT), Non-enhanced CT (NCT) and angiography were performed within 6hours post-ictus. Perfusion maps were generated using a maximum slope (MS) and a deconvolution-based approach (DC). Two blinded neuroradiologists independently evaluated MS and DC maps regarding vasospasm-related perfusion impairment on a 3-point Likert-scale (0=no impairment, 1=impairment affecting <50%, 2=impairment affecting >50% of vascular territory). A third independent neuroradiologist assessed angiography for presence and severity of arterial narrowing on a 3-point Likert scale (0=no narrowing, 1=narrowing affecting <50%, 2=narrowing affecting>50% of artery diameter). MS and DC perfusion maps were evaluated regarding diagnostic accuracy for angiographical arterial spasm with angiography as reference standard. Correlation analysis of angiography findings with both MS and DC perfusion maps was additionally performed. Furthermor, the agreement between MS and DC and inter-reader agreement was assessed.

Results: DC maps yielded significantly higher diagnostic accuracy than MS perfusion maps (DC:AUC=.870; MS:AUC=.805; P=0.007) with higher sensitivity for DC compared to MS (DC:sensitivity=.758; MS:sensitivity=.625). DC maps revealed stronger correlation with angiography than MS (DC: R=.788; MS: R=694;=<0.001). MS and DC showed substantial agreement (Kappa=.626). Regarding inter-reader analysis, (almost) perfect inter-reader agreement was observed for both MS and DC maps (Kappa≥981).

Conclusion: DC yields significantly higher diagnostic accuracy for the detection of angiographic arterial spasm and higher correlation with angiographic findings compared to MS.
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September 2018

Relationship between low tube voltage (70 kV) and the iodine delivery rate (IDR) in CT angiography: An experimental in-vivo study.

PLoS One 2017 20;12(3):e0173592. Epub 2017 Mar 20.

MR and CT Contrast Media Research, Bayer Healthcare, Berlin, Germany.

Objective: Very short acquisition times and the use of low-kV protocols in CTA demand modifications in the contrast media (CM) injection regimen. The aim of this study was to optimize the use of CM delivery parameters in thoraco-abdominal CTA in a porcine model.

Materials And Methods: Six pigs (55-68 kg) were examined with a dynamic CTA protocol (454 mm scan length, 2.5 s temporal resolution, 70 s total acquisition time). Four CM injection protocols were applied in a randomized order. 120 kV CTA protocol: (A) 300 mg iodine/kg bodyweight (bw), IDR = 1.5 g/s (flow = 5 mL/s), injection time (ti) 12 s (60 kg bw). 70 kV CTA protocols: 150 mg iodine/kg bw: (B) IDR = 0.75 g/s (flow = 2.5 mL/s), ti = 12 s (60 kg bw); (C) IDR = 1.5 g/s (flow = 5 mL/s), ti = 12 s (60 kg bw); (D) IDR = 3.0 g/s (flow = 10 mL/s), ti = 3 s (60 kg bw). The complete CM bolus shape was monitored by creating time attenuation curves (TAC) in different vascular territories. Based on the TAC, the time to peak (TTP) and the peak enhancement were determined. The diagnostic window (relative enhancement > 300 HU), was calculated and compared to visual inspection of the corresponding CTA data sets.

Results: The average relative arterial peak enhancements after baseline correction were 358.6 HU (A), 356.6 HU (B), 464.0 HU (C), and 477.6 HU (D). The TTP decreased with increasing IDR and decreasing ti, protocols A and B did not differ significantly (systemic arteries, p = 0.843; pulmonary arteries, p = 0.183). The delay time for bolus tracking (trigger level 100 HU; target enhancement 300 HU) for single-phase CTA was comparable for protocol A and B (3.9, 4.3 s) and C and D (2.4, 2.0 s). The scan window time frame was comparable for the different protocols by visual inspection of the different CTA data sets and by analyzing the TAC.

Conclusions: All protocols provided sufficient arterial enhancement. The use of a 70 kV CTA protocol is recommended because of a 50% reduction of total CM volume and a 50% reduced flow rate while maintaining the bolus profile. In contrast to pulmonary arterial enhancement, the systemic arterial enhancement improved only slightly increasing the IDR from 1.5 g/s to 3 g/s because of bolus dispersion of the very short bolus (3s) in the lungs.
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August 2017

Iodine concentration as a perfusion surrogate marker in oncology: Further elucidation of the underlying mechanisms using Volume Perfusion CT with 80 kVp.

Eur Radiol 2016 Sep 17;26(9):2929-36. Epub 2015 Dec 17.

Department of Radiology, Diagnostic and Interventional Radiology, Eberhard Karls University, Hoppe-Seyler-Str. 3, D-72076, Tübingen, Germany.

Objectives: To assess the value of iodine concentration (IC) in computed tomography data acquired with 80 kVp, as a surrogate for perfusion imaging in hepatocellular carcinoma (HCC) and lymphoma by comparing iodine related attenuation (IRA) with quantitative Volume Perfusion CT (VPCT)-parameters.

Methods: VPCT-parameters were compared with intra-tumoral IC at 5 time points after the aortic peak enhancement (APE) with a temporal resolution of 3.5 sec in untreated 30 HCC and 30 lymphoma patients.

Results: Intra-tumoral perfusion parameters for HCC showed a blood flow (BF) of 52.7 ± 17.0 mL/100 mL/min, blood volume (BV) 12.6 ± 4.3 mL/100 mL, arterial liver perfusion (ALP) 44.4 ± 12.8 mL/100 mL/min. Lesion IC 7 sec after APE was 133.4 ± 57.3 mg/100 mL. Lymphoma showed a BF of 36.8 ± 13.4 mL/100 mL/min, BV of 8.8 ± 2.8 mL/100 mL and IC of 118.2 ± 64.5 mg/100 mL 3.5 sec after APE. Strongest correlations exist for VPCT-derived BF and ALP with IC in HCC 7 sec after APE (r = 0.71 and r = 0.84) and 3.5 sec after APE in lymphoma lesions (r = 0.77). Significant correlations are also present for BV (r = 0.60 and r = 0.65 for HCC and lymphoma, respectively).

Conclusions: We identified a good, time-dependent agreement between VPCT-derived flow values and IC in HCC and lymphoma. Thus, CT-derived ICs 7 sec after APE in HCC and 3.5 sec in lymphoma may be used as surrogate imaging biomarkers for tumor perfusion with 80 kVp.

Key Points: • Iodine concentration derived from low kVp CT is regarded as perfusion surrogate • Correlation with Perfusion CT was performed to elucidate timing and histology dependencies • Highest correlation was present 7 sec after aortic peak enhancement in hepatocellular carcinoma • In lymphoma, highest correlation was calculated 3.5 sec after aortic peak enhancement • With these results, further optimization of Dual energy CT protocols is possible.
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September 2016

Automated Tube Voltage Selection for Radiation Dose Reduction in CT Angiography Using Different Contrast Media Concentrations and a Constant Iodine Delivery Rate.

AJR Am J Roentgenol 2015 Dec;205(6):1332-8

2 CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, The Netherlands.

Objective: The purpose of this study was to systematically investigate radiation dose reduction using automated tube voltage selection during CT angiography (CTA) and to evaluate the impact of contrast medium (CM) injection protocols on dose reduction.

Materials And Methods: A circulation phantom containing the thoracic and abdominal vasculature was used. Four different concentrations of CM (iopromide 300 and 370 mg I/mL and iomeprol 350 and 400 mg I/mL) were administered while maintaining an identical iodine delivery rate (1.8 g I/s) and total iodine load (20.0 g). Three different scanning protocols for CTA of the thoracoabdominal aorta were used: protocol A, no dose modulation; protocol B, automated tube current modulation (CARE Dose4D); and protocol C, automated tube voltage selection (CARE kV). The dose-length product was recorded to calculate the effective dose. Attenuation values (in Hounsfield units), image noise levels, and signal-to-noise ratios (SNRs) in six predefined intravascular sites (three thoracic and three abdominal) were measured by two readers. All values were analyzed using the Kruskal-Wallis test and two-way ANOVA.

Results: There was a significant reduction in the effective dose (in millisieverts) for protocols B (mean ± SD, 2.03 ± 0.1 mSv) and C (1.00 ± 0.0 mSv) compared with protocol A (4.34 ± 0.0 mSv). The dose was reduced by 53% for protocol B and by 77% for protocol C. No significant differences were found in the effective dose among the different CM injection protocols within the scanning protocols; all p values were > 0.05. The attenuation values and SNRs were comparable among all the different CM injection protocols; all p values were > 0.05.

Conclusion: A large radiation dose reduction (77%) can be achieved using automated tube voltage selection independent of the CM injection protocol.
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December 2015

Development of an Ex Vivo, Beating Heart Model for CT Myocardial Perfusion.

Biomed Res Int 2015 21;2015:412716. Epub 2015 Jun 21.

University of Groningen, University Medical Center Groningen, Center for Medical Imaging-North East Netherlands, Department of Radiology, Hanzeplein 1, 9713 GZ Groningen, Netherlands.

Objective: To test the feasibility of a CT-compatible, ex vivo, perfused porcine heart model for myocardial perfusion CT imaging.

Methods: One porcine heart was perfused according to Langendorff. Dynamic perfusion scanning was performed with a second-generation dual source CT scanner. Circulatory parameters like blood flow, aortic pressure, and heart rate were monitored throughout the experiment. Stenosis was induced in the circumflex artery, controlled by a fractional flow reserve (FFR) pressure wire. CT-derived myocardial perfusion parameters were analysed at FFR of 1 to 0.10/0.0.

Results: CT images did not show major artefacts due to interference of the model setup. The pacemaker-induced heart rhythm was generally stable at 70 beats per minute. During most of the experiment, blood flow was 0.9-1.0 L/min, and arterial pressure varied between 80 and 95 mm/Hg. Blood flow decreased and arterial pressure increased by approximately 10% after inducing a stenosis with FFR ≤ 0.50. Dynamic perfusion scanning was possible across the range of stenosis grades. Perfusion parameters of circumflex-perfused myocardial segments were affected at increasing stenosis grades.

Conclusion: An adapted Langendorff porcine heart model is feasible in a CT environment. This model provides control over physiological parameters and may allow in-depth validation of quantitative CT perfusion techniques.
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April 2016

Technical prerequisites and imaging protocols for CT perfusion imaging in oncology.

Eur J Radiol 2015 Dec 24;84(12):2359-67. Epub 2015 Jun 24.

Institute of Clinical Radiology and Nuclear Medicine, University Medical Center, Medical Faculty Mannheim, Heidelberg University, Germany. Electronic address:

The aim of this review article is to define the technical prerequisites of modern state-of-the-art CT perfusion imaging in oncology at reasonable dose levels. The focus is mainly on abdominal and thoracic tumor imaging, as they pose the largest challenges with respect to attenuation and patient motion. We will show that low kV dynamic scanning in conjunction with detection technology optimized for low photon fluxes has the highest impact on reducing dose independently of other choices made in the protocol selection. We discuss, derived from relatively simple first principles, on what appropriate temporal sampling and total scan duration depend on and why optimized contrast medium injection protocols are also essential in limiting dose. Finally we will examine the possibility of simultaneously extracting standard morphological and functional information from one single 4D examination as a potential enabler for a more widespread use of dynamic contrast enhanced CT in oncology.
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December 2015

Dynamic volume perfusion CT in patients with lung cancer: baseline perfusion characteristics of different histological subtypes.

Eur J Radiol 2013 Dec 11;82(12):e894-900. Epub 2013 Sep 11.

Department of Radiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, China; Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address:

Objective: To evaluate dynamic volume perfusion CT (dVPCT) tumor baseline characteristics of three different subtypes of lung cancer in untreated patients.

Materials And Methods: 173 consecutive patients (131 men, 42 women; mean age 61 ± 10 years) with newly diagnosed lung cancer underwent dVPCT prior to biopsy. Tumor permeability, blood flow (BF), blood volume (BV) and mean transit time (MTT) were quantitatively assessed as well as tumor diameter and volume. Tumor subtypes were histologically determined and compared concerning their dVPCT results. dVPCT results were correlated to tumor diameter and volume.

Results: Histology revealed adenocarcinoma in 88, squamous cell carcinoma in 54 and small cell lung cancer (SCLC) in 31 patients. Tumor permeability was significantly differing between adenocarcinoma, squamous cell carcinoma and SCLC (all p<0.05). Tumor BF and BV were higher in adenocarcinomathan in SCLC (p = 0.001 and p=0.0002 respectively). BV was also higher in squamous cell carcinoma compared to SCLC (p = 0.01). MTT was not differing between tumor subtypes. Regarding all tumors, tumor diameter did not correlate with any of the dVPCT parameters, whereas tumor volume was negatively associated with permeability, BF and BV (r = -0.22, -0.24, -0.24, all p<0.05). In squamous cell carcinoma, tumor diameter und volume correlated with BV (r = 0.53 and r = -0.40, all p<0.05). In SCLC, tumor diameter und volume correlated with MTT (r = 0.46 and r = 0.39, all p<0.05). In adenocarcinoma, no association between morphological and functional tumor characteristics was observed.

Conclusions: dVPCT parameters are only partially related to tumor diameter and volume and are significantly differing between lung cancer subtypes.
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December 2013

Diagnostic performance of whole brain volume perfusion CT in intra-axial brain tumors: preoperative classification accuracy and histopathologic correlation.

Eur J Radiol 2012 Dec 7;81(12):4105-11. Epub 2012 Sep 7.

Department of Neuroradiology, Georg-August University, University Hospital of Goettingen, Robert-Koch Strasse 40, 37075 Goettingen, Germany.

Background: To evaluate the preoperative diagnostic power and classification accuracy of perfusion parameters derived from whole brain volume perfusion CT (VPCT) in patients with cerebral tumors.

Methods: Sixty-three patients (31 male, 32 female; mean age 55.6 ± 13.9 years), with MRI findings suspected of cerebral lesions, underwent VPCT. Two readers independently evaluated VPCT data. Volumes of interest (VOIs) were marked circumscript around the tumor according to maximum intensity projection volumes, and then mapped automatically onto the cerebral blood volume (CBV), flow (CBF) and permeability Ktrans perfusion datasets. A second VOI was placed in the contra lateral cortex, as control. Correlations among perfusion values, tumor grade, cerebral hemisphere and VOIs were evaluated. Moreover, the diagnostic power of VPCT parameters, by means of positive and negative predictive value, was analyzed.

Results: Our cohort included 32 high-grade gliomas WHO III/IV, 18 low-grade I/II, 6 primary cerebral lymphomas, 4 metastases and 3 tumor-like lesions. Ktrans demonstrated the highest sensitivity, specificity and positive predictive value, with a cut-off point of 2.21 mL/100mL/min, for both the comparisons between high-grade versus low-grade and low-grade versus primary cerebral lymphomas. However, for the differentiation between high-grade and primary cerebral lymphomas, CBF and CBV proved to have 100% specificity and 100% positive predictive value, identifying preoperatively all the histopathologically proven high-grade gliomas.

Conclusion: Volumetric perfusion data enable the hemodynamic assessment of the entire tumor extent and provide a method of preoperative differentiation among intra-axial cerebral tumors with promising diagnostic accuracy.
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December 2012

Brain volume perfusion CT performed with 128-detector row CT system in patients with cerebral gliomas: a feasibility study.

Eur Radiol 2011 Sep 15;21(9):1811-9. Epub 2011 May 15.

Department of Neuroradiology, Georg-August University, University Hospital of Goettingen, Robert-Koch Str. 40, 37075 Goettingen, Germany.

Objectives: Validation of the feasibility and efficacy of volume perfusion computed tomography (VPCT) in the preoperative assessment of cerebral gliomas by applying a 128-slice CT covering the entire tumour.

Methods: Forty-six patients (25 men, 21 women; mean age 52.8 years) with cerebral gliomas were evaluated with VPCT. Two readers independently evaluated VPCT data, drawing volumes of interest (VOIs) around the tumour according to maximum intensity projection volumes, which were mapped automatically onto the cerebral blood volume (CBV), flow (CBF) and permeability (Ktrans) perfusion datasets. As control, a second VOI was placed in the contralateral healthy cortex. Correlation among perfusion parameters, tumour grade, hemisphere and VOIs was assessed. The diagnostic power of perfusion parameters was analysed by receiver operating characteristics curve analyses.

Results: VPCT was feasible in the assessment of the entire tumour extent. Mean values of Ktrans, CBV, CBF in high-grade gliomas were significantly higher compared with low-grade (p < 0.01). Ktrans demonstrated the highest diagnostic (97% sensitivity), positive (100%) and negative (94%) prognostic values.

Conclusions: VPCT was feasible in all subjects. All areas of different perfusion characteristics are depicted and quantified in colour-coded 3D maps. The derived parameters correlate well with tumour histopathology, differentiating low- from high-grade gliomas.
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September 2011

Comment on "Developing DCE-CT to quantify intra-tumor heterogeneity in breast tumors with differing angiogenic phenotype".

IEEE Trans Med Imaging 2010 Apr;29(4):1088-9; author reply 1089-92

In our comment some essential issues concerning determination of arterial input function (AIF), cardiac and respiratory related motion artifacts, contrast agent application and compartmental model fitting done by Cao et al., 2009 are discussed.
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April 2010

Preliminary assessment of dynamic contrast-enhanced CT implementation in pretreatment FDG-PET/CT for outcome prediction in head and neck tumors.

Acta Radiol 2010 Sep;51(7):793-9

Dresden University of Technology, Germany.

Background: Recently published data show some controversy concerning the impact of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in predicting head and neck tumors (HNT) outcome. Assessment of tumor blood supply parameters using dynamic contrast-enhanced CT (DCE-CT) may deliver additional information concerning this important question.

Purpose: To evaluate the contribution of DCE-CT implemented in pretherapeutic FDG-PET/CT protocol for prognosis prediction in patients with HNT.

Material And Methods: Ten consecutive patients (median age 50 years, range 47-74 years) with histologically proven HNT underwent FDG-PET/CT with DCE-CT before treatment. FDG uptake was measured by maximum standardized uptake value (SUV(max)). Relative tumor blood volume (rTBV) was determined from DCE-CT using Patlak analysis. Intratumoral heterogeneity was assessed by means of lacunarity analysis. Obtained values were compared with time-to-progression and overall survival. PET and DCE-CT images were compared on a pixel-by-pixel basis using Pearson coefficient of correlation.

Results: Three patients with lower FDG uptake (SUV(max): 8+/-1) and five patients with higher FDG uptake (SUV(max): 15+/-4, P=0.004) were free of local recurrence for 24 months. Two groups of patients with significantly differing lower (group A: 0.37+/-0.02, n=6) and higher (group B: 0.52+/-0.01, n=4; P<0.01), tumor heterogeneity (lacunarity) were identified. Corresponding mean rTBV was higher in group A (9.6+/-1.8 ml/100 ml) than in group B (6.2+/-0.6 ml/100 ml). All six patients with homogeneous tumor blood supply (lower lacunarity) and higher rTBV were free of local recurrence during 24 months, while two of four patients with heterogeneous tumor blood supply (higher lacunarity) and lower rTBV died during follow-up due to tumor relapse. A weak correlation between FDG-PET and DCE-CT rTBV was observed (R(2)=0.1).

Conclusion: FDG-PET/CT and DCT-CT are complementary methods for surveillance assessment in patients with HNT. Implementation of DCE-CT in the pretreatment FDG-PET/CT protocol may improve tumor outcome prediction.
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September 2010

Performance assessment of dynamic spiral scan modes with variable pitch for quantitative perfusion computed tomography.

Invest Radiol 2010 Jul;45(7):378-86

OncoRay-Center for Radiation Research in Oncology, TU Dresden, Germany.

Purpose: Perfusion computed tomography is increasingly being used in diagnostic radiology. Axial coverage of the traditional approach is limited to the width of the detector. Using continuous periodic table movement coverage can be increased beyond this limit. In this study, we compared tissue flow values determined from scans with a periodic spiral implementation with variable pitch with ones determined from standard dynamic scan modes.

Methods: A flow phantom (preserved porcine kidney) was scanned with 2 settings of a periodic spiral (Adaptive 4D Spiral) with a range of 100 and 148 mm and a temporal sampling of 1.5 seconds. Additionally, the whole phantom was scanned with the standard dynamic mode (detector width 38.4 mm, temporal sampling 1.0 seconds) at various overlapping positions as a reference. Scan parameters (80 kV, 140 mAs, 40s scan time) were selected similar to a typical brain perfusion study. All scans were repeated 5 times. Tissue flow was calculated with a dedicated deconvolution algorithm. In a center slice and 3 additional slices at various off center positions flow values were recorded in a total of 126 regions of interest (ROI). Reproducibility was determined from the variation of the repeat scans. Agreement between periodic spirals and standard mode was determined by Bland Altman plots and correlation analysis.

Results: The reproducibility of the tissue flow determination ranged from 2.7 to 4.4 mL/100 mL/min and was similar for all scan modes. The coefficient of variation ranged from 3.9% to 6.1%. Mean tissue flow in the 126 ROIs ranged from 35 to 121 mL/100 mL/min. There was excellent correlation between both periodic spiral ranges and the standard dynamic mode with a Pearson correlation coefficient of r = 0.97. The regression slope (intercept 0) for the 100 mm range was 1.01, for the 148 mm range it was 0.97. The absolute differences per ROI varied between 1.5 and 4.1 mL/100 mL/min, the relative differences between 1.9% and 6.5%. Differences did not depend on the slice location.

Conclusions: Periodic spiral scan modes with variable pitch and a sampling rate of 1.5 seconds can be used for the quantitative determination of tissue flow. Their performance is equivalent to equidistant sampling with standard dynamic scan modes. The ranges of 100 and 148 mm investigated allow coverage of the whole brain or an entire organ for perfusion imaging.
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July 2010

Quantitative whole heart stress perfusion CT imaging as noninvasive assessment of hemodynamics in coronary artery stenosis: preliminary animal experience.

Invest Radiol 2010 Jun;45(6):298-305

Department of Diagnostic Radiology, University Hospital, RWTH Aachen University, Aachen, Germany.

Purpose: To quantify differences in regional myocardial perfusion in coronary artery stenosis by the use of dual source computed tomography (DSCT) in an animal model.

Material And Methods: In 5 pigs, an 80% stenosis of the left anterior descending artery was successfully induced by partial balloon occlusion (ischemia group). Five animals served as control group. All animals underwent contrast enhanced whole heart DSCT (Definition Flash, Siemens, Germany) perfusion imaging using a prototype electrocardiogram -triggered dynamic scan mode. Imaging was performed at rest as well as under stress conditions during continuous infusion of adenosine (240 mg/kg/min). For contrast enhancement 60 mL Iopromide 300 (Ultravist 300, Bayer-Schering Pharma, Berlin, Germany) were injected at a rate of 6 mL/s. Myocardial blood flow (MBF), first pass distribution volume, and intravascular blood volume were volumetrically quantified.

Results: In the control group MBF increased significantly from 98.2 mL/100 mL/min to 134.0 mL/100 mL/min if adenosine was administered (P = 0.0153). There were no significant differences in the perfusion parameters comparing the control and ischemia group at rest. In the ischemia group MBF under stress was 74.0 +/- 21.9 mL/100 mL/min in the poststenotic myocardium and 117.4 +/- 18.6 mL/100 mL/min in the remaining normal myocardium (P = 0.0024).

Conclusion: DSCT permits quantitative whole heart perfusion imaging. As this technique is able to show the hemodynamic effect of high grade coronary artery stenosis, it exceeds the present key limitation of cardiac computed tomography, which currently only allows a morphologic assessment of coronary artery stenosis.
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June 2010

Partial scan artifact reduction (PSAR) for the assessment of cardiac perfusion in dynamic phase-correlated CT.

Med Phys 2009 Dec;36(12):5683-94

Institute of Medical Physics, Erlangen, Germany.

Purpose: Cardiac CT achieves its high temporal resolution by lowering the scan range from 2pi to pi plus fan angle (partial scan). This, however, introduces CT-value variations, depending on the angular position of the pi range. These partial scan artifacts are of the order of a few HU and prevent the quantitative evaluation of perfusion measurements. The authors present the new algorithm partial scan artifact reduction (PSAR) that corrects a dynamic phase-correlated scan without a priori information.

Methods: In general, a full scan does not suffer from partial scan artifacts since all projections in [0, 2pi] contribute to the data. To maintain the optimum temporal resolution and the phase correlation, PSAR creates an artificial full scan pn(AF) by projectionwise averaging a set of neighboring partial scans pn(P) from the same perfusion examination (typically N approximately 30 phase-correlated partial scans distributed over 20 s and n = 1, ..., N). Corresponding to the angular range of each partial scan, the authors extract virtual partial scans pn(V) from the artificial full scan pn(AF). A standard reconstruction yields the corresponding images fn(P), fn(AF), and fn(V). Subtracting the virtual partial scan image fn(V) from the artificial full scan image fn(AF) yields an artifact image that can be used to correct the original partial scan image: fn(C) = fn(P) - fn(V) + fn(AF), where fn(C) is the corrected image.

Results: The authors evaluated the effects of scattered radiation on the partial scan artifacts using simulated and measured water phantoms and found a strong correlation. The PSAR algorithm has been validated with a simulated semianthropomorphic heart phantom and with measurements of a dynamic biological perfusion phantom. For the stationary phantoms, real full scans have been performed to provide theoretical reference values. The improvement in the root mean square errors between the full and the partial scans with respect to the errors between the full and the corrected scans is up to 54% for the simulations and 90% for the measurements.

Conclusions: The phase-correlated data now appear accurate enough for a quantitative analysis of cardiac perfusion.
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December 2009

A biological phantom for contrast-media-based perfusion studies with CT.

Invest Radiol 2009 Oct;44(10):676-82

OncoRay-Center for Radiation Research in Oncology, TU Dresden, Germany.

Objectives: Perfusion computed tomography (PCT) is increasingly getting popular with the advent of computed tomography (CT) systems with adequate temporal resolution and spatial coverage. We sought to develop a biological phantom for perfusion measurements in CT to design, improve, and validate scan protocols and postprocessing algorithms in vitro.

Materials And Methods: A special technique was applied to prepare and preserve a fresh porcine kidney. The kidney was connected to an open circuit driven by a peristaltic pump with the option to inject contrast material. We evaluated repeated dynamic contrast-enhanced CT acquisitions with different input flow rates and the relation to calculated parenchymal flow results of the phantom. Flow was calculated with 2 different algorithms. Identical scans were performed with a time interval of 1 year to check long-term stability of the phantom. Different bolus geometries were designed and bolus dispersion was measured for the setup using a tubing array.

Results: We found a linear relationship between the input flow rate of the circuit and the calculated phantom tissue flow with a correlation coefficient rr2 = 0.99 for both algorithms. Both algorithms resulted in very similar absolute values, the mean difference was 3.1 mL/100 mL/min. Perfusion measurements with contrast material injection and storage did not alter the phantom. The enhancement properties did not change over the time of 1 year. With our setup, it was possible to design typical bolus geometries as they occur in clinical practice. Bolus dispersion was small: peak enhancement and bolus width changed by about only 5% over 2-m tube length.

Conclusions: A phantom for parenchymal flow measurements suitable for repeated measurements over a long period of time was developed. The setup allows the design of diverse bolus geometries with negligible dispersion.
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October 2009

Lesion to the nigrostriatal dopamine system disrupts stimulus-response habit formation.

J Neurosci 2005 Mar;25(11):2771-80

Laboratoire de Neurobiologie de l'Apprentissage, de la Mémoire et de la Communication, Unité Mixte de Recherche 8620, Université Paris Sud, 91405 Orsay Cedex, France.

Acquisition and performance of instrumental actions are assumed to require both action-outcome and stimulus-response (S-R) habit processes. Over the course of extended training, control over instrumental performance shifts from goal-directed action-outcome associations to S-R associations that progressively gain domination over behavior. Lesions of the lateral part of the dorsal striatum disrupt this process, and rats with lesions to the lateral striatum showed selective sensitivity to devaluation of the instrumental outcome (Yin et al., 2004), indicating that this area is necessary for habit formation. The present experiment further explored the basis of this dysfunction by examining the ability of rats subjected to bilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic pathway to develop behavioral autonomy with overtraining. Rats were given extended training on two cued instrumental tasks associating a stimulus (a tone or a light) with an instrumental action (lever press or chain pull) and a food reward (pellets or sucrose). Both tasks were run daily in separate sessions. Overtraining was followed by a test of goal sensitivity by satiety-specific devaluation of the reward. In control animals, one action (lever press) was insensitive to reward devaluation, indicating that it became a habit, whereas the second action (chain pull) was still sensitive to goal devaluation. This result provides evidence that the development of habit learning may depend on the characteristics of the response. In dopamine-depleted rats, lever press and chain pull remained sensitive to reward devaluation, evidencing a role of striatal dopamine transmission in habit formation.
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March 2005