Jens Maus

The PET-derived tumor-to-blood standard uptake ratio (SUR) is superior to tumor SUV as a surrogate parameter of the metabolic rate of FDG

BackgroundThe standard uptake value (SUV) approach in oncological positron emission tomography has known shortcomings, all of which affect the reliability of the SUV as a surrogate of the targeted quantity, the metabolic rate of [18F]fluorodeoxyglucose (FDG), Km. Among the shortcomings are time dependence, susceptibility to errors in scanner and dose calibration, insufficient correlation between systemic distribution volume and body weight, and, consequentially, residual inter-study variability of the arterial input function (AIF) despite SUV normalization. Especially the latter turns out to be a crucial factor adversely affecting the correlation between SUV and Km and causing inter-study variations of tumor SUVs that do not reflect actual changes of the metabolic uptake rate. In this work, we propose to replace tumor SUV by the tumor-to-blood standard uptake ratio (SUR) in order to distinctly improve the linear correlation with Km.MethodsAssuming irreversible FDG kinetics, SUR can be expected to exhibit a much better linear correlation to Km than SUV. The theoretical derivation for this prediction is given and evaluated in a group of nine patients with liver metastases of colorectal cancer for which 15 fully dynamic investigations were available and Km could thus be derived from conventional Patlak analysis.ResultsFor any fixed time point T at sufficiently late times post injection, the Patlak equation predicts a linear correlation between SUR and Km under the following assumptions: (1) approximate shape invariance (but arbitrary scale) of the AIF across scans/patients and (2) low variability of the apparent distribution volume Vr (the intercept of the Patlak Plot). This prediction - and validity of the underlying assumptions - has been verified in the investigated patient group. Replacing tumor SUVs by SURs does improve the linear correlation of the respective parameter with Km from r = 0.61 to r = 0.98.ConclusionsSUR is an easily measurable parameter that is highly correlated to Km. In this respect, it is clearly superior to SUV. Therefore, SUR should be seriously considered as a drop-in replacement for SUV-based approaches.

FDG PET/MR for lymph node staging in head and neck cancer

OBJECTIVE To assess the diagnostic value of PET/MR (positron emission tomography/magnetic resonance imaging) with FDG (18F-fluorodeoxyglucose) for lymph node staging in head and neck cancer. MATERIALS AND METHODS This prospective study was approved by the local ethics committee; all patients signed informed consent. Thirty-eight patients with squamous cell carcinoma of the head and neck region underwent a PET scan on a conventional scanner and a subsequent PET/MR on a whole-body hybrid system after a single intravenous injection of FDG. The accuracy of PET, MR and PET/MR for lymph node metastases were compared using receiver operating characteristic (ROC) analysis. Histology served as the reference standard. RESULTS Metastatic disease was confirmed in 16 (42.1%) of 38 patients and 38 (9.7%) of 391 dissected lymph node levels. There were no significant differences between PET/MR, MR and PET and MR (p>0.05) regarding accuracy for cervical metastatic disease. Based on lymph node levels, sensitivity and specificity for metastatic involvement were 65.8% and 97.2% for MR, 86.8% and 97.0% for PET and 89.5% and 95.2% for PET/MR. CONCLUSIONS In head and neck cancer, FDG PET/MR does not significantly improve accuracy for cervical lymph node metastases in comparison to MR or PET.

Correction of scan time dependence of standard uptake values in oncological PET

BackgroundStandard uptake values (SUV) as well as tumor-to-blood standard uptake ratios (SUR) measured with [ 18F-]fluorodeoxyglucose (FDG) PET are time dependent. This poses a serious problem for reliable quantification since variability of scan start time relative to the time of injection is a persistent issue in clinical oncological Positron emission tomography (PET). In this work, we present a method for scan time correction of, both, SUR and SUV.MethodsAssuming irreversible FDG kinetics, SUR is linearly correlated to Km (the metabolic rate of FDG), where the slope only depends on the shape of the arterial input function (AIF) and on scan time. Considering the approximately invariant shape of the AIF, this slope (the ‘Patlak time’) is an investigation independent function of scan time. This fact can be used to map SUR and SUV values from different investigations to a common time point for quantitative comparison. Additionally, it turns out that modelling the invariant AIF shape by an inverse power law is possible which further simplifies the correction procedure. The procedure was evaluated in 15 fully dynamic investigations of liver metastases from colorectal cancer and 10 dual time point (DTP) measurements. From each dynamic study, three ‘static scans’ at T=20,35,and 55 min post injection (p.i.) were created, where the last scan defined the reference time point to which the uptake values measured in the other two were corrected. The corrected uptake values were then compared to those actually measured at the reference time. For the DTP studies, the first scan (acquired at (78.1 ± 15.9) min p.i.) served as the reference, and the uptake values from the second scan (acquired (39.2 ± 9.9) min later) were corrected accordingly and compared to the reference.ResultsFor the dynamic data, the observed difference between uncorrected values and values at reference time was (-52±4.5)% at T=20 min and (-31±3.7)% at T=35 min for SUR and (-30±6.6)% at T=20 min and (-16±4)% at T=35 min for SUV. After correction, the difference was reduced to (-2.9±6.6)% at T=20 min and (-2.7±5)% at T=35 min for SUR and (1.9% ± 6.2)% at T=20 min and (1.7 ± 3.3)% at T=35 min for SUV. For the DTP studies, the observed differences of SUR and SUV between late and early scans were (48 ± 11)% and (24 ± 8.4)%, respectively. After correction, these differences were reduced to (2.6 ± 6.9)% and (-2.4±7.3)%, respectively.ConclusionIf FDG kinetics is irreversible in the targeted tissue, correction of SUV and SUR for scan time variability is possible with good accuracy. The correction distinctly improves comparability of lesion uptake values measured at different times post injection.

FDG PET/MR for the assessment of lymph node involvement in lymphoma: initial results and role of diffusion-weighted MR.

RATIONALE AND OBJECTIVES The purpose of this study was to evaluate the sensitivity and specificity of positron emission tomography/magnetic resonance imaging (PET/MR) with 18F-fluorodeoxyglucose (FDG) for nodal involvement in malignant lymphoma. MATERIALS AND METHODS Twenty-seven patients with malignant lymphoma (16 men and 11 women; mean age, 45 years) were included in this retrospective study. The patients underwent FDG PET/MR after intravenous injection of FDG (176-357 MBq FDG, 282 MBq on average). Follow-up imaging and histology served as the standard of reference. RESULTS One-hundred and twenty-seven (18.1%) of 702 lymph node stations were rated as having lymphoma involvement based on the standard of reference. One-hundred and twenty-four (17.7%) of 702 lymph node stations were rated as positive by FDG PET/MR. The sensitivity and specificity of FDG PET/MR for lymph node station involvement were 93.8% and 99.4%. CONCLUSIONS FDG PET/MR is feasible for lymphoma staging and has a high sensitivity and specificity for nodal involvement in lymphoma. Comparison with PET/CT is necessary to determine whether FDG PET/MR can replace PET/CT for lymphoma staging.

Early and late effects of radiochemotherapy on cerebral blood flow in glioblastoma patients measured with non-invasive perfusion MRI.

BACKGROUND AND PURPOSE To provide a systematic measure of changes of brain perfusion in healthy tissue following a fractionated radiotherapy of brain tumors. MATERIALS AND METHODS Perfusion was assessed before and after radiochemotherapy using arterial spin labeling in a group of 24 patients (mean age 54.3 ± 14.1 years) with glioblastoma multiforme. Mean relative perfusion change in gray matter in the hemisphere contralateral to the tumor was obtained for the whole hemisphere and also for six regions created by thresholding the individual dose maps at 10 Gy steps. RESULTS A significant decrease of perfusion of -9.8 ± 20.9% (p=0.032) compared to the pre-treatment baseline was observed 3 months after the end of radiotherapy. The decrease was more pronounced for high-dose regions above 50 Gy (-16.8 ± 21.0%, p=0.0014) than for low-dose regions below 10 Gy (-2.3 ± 20.0%, p=0.54). No further significant decrease compared to the post-treatment baseline was observed 6 months (-0.4 ± 18.4%, p=0.94) and 9 months (2.0 ± 15.4%, p=0.74) after the end of radiotherapy. CONCLUSIONS Perfusion decreased significantly during the course of radiochemotherapy. The decrease was higher in regions receiving a higher dose of radiation. This suggests that the perfusion decrease is at least partly caused by radiotherapy. Our results suggest that the detrimental effects of radiochemotherapy on perfusion occur early rather than later.

A volume of intersection approach for on-the-fly system matrix calculation in 3D PET image reconstruction.

The aim of this study is the evaluation of on-the-fly volume of intersection computation for systems geometry modelling in 3D PET image reconstruction. For this purpose we propose a simple geometrical model in which the cubic image voxels on the given Cartesian grid are approximated with spheres and the rectangular tubes of response (ToRs) are approximated with cylinders. The model was integrated into a fully 3D list-mode PET reconstruction for performance evaluation. In our model the volume of intersection between a voxel and the ToR is only a function of the impact parameter (the distance between voxel centre to ToR axis) but is independent of the relative orientation of voxel and ToR. This substantially reduces the computational complexity of the system matrix calculation. Based on phantom measurements it was determined that adjusting the diameters of the spherical voxel size and the ToR in such a way that the actual voxel and ToR volumes are conserved leads to the best compromise between high spatial resolution, low noise, and suppression of Gibbs artefacts in the reconstructed images. Phantom as well as clinical datasets from two different PET systems (Siemens ECAT HR(+) and Philips Ingenuity-TF PET/MR) were processed using the developed and the respective vendor-provided (line of intersection related) reconstruction algorithms. A comparison of the reconstructed images demonstrated very good performance of the new approach. The evaluation showed the respective vendor-provided reconstruction algorithms to possess 34-41% lower resolution compared to the developed one while exhibiting comparable noise levels. Contrary to explicit point spread function modelling our model has a simple straight-forward implementation and it should be easy to integrate into existing reconstruction software, making it competitive to other existing resolution recovery techniques.

FDG PET/MR in initial staging of sarcoma: Initial experience and comparison with conventional imaging

OBJECTIVE To assess the feasibility of positron emission tomography/magnetic resonance imaging (PET/MR) with 18F-fluordeoxyglucose (FDG) for initial staging of sarcoma. MATERIALS AND METHODS Twenty-nine patients with sarcoma were included in this study. Weighted kappa (κ) was used to assess the agreement between PET/MR and conventional imaging (CT and MR). The accuracy of PET/MR and conventional imaging for distant metastases was compared using receiver operating characteristic (ROC) analysis. RESULTS T and M stage were identical for PET/MR and conventional modalities in all patients (κ=1). N stage was identical for 28/29 patients (κ=0.65). CONCLUSIONS FDG PET/MR shows excellent agreement with the currently preferred imaging methods (CT and MR) in initial staging of sarcoma.

Correction of quantification errors in pelvic and spinal lesions caused by ignoring higher photon attenuation of bone in [18F]NaF PET/MR.

PURPOSE MR-based attenuation correction (MRAC) in routine clinical whole-body positron emission tomography and magnetic resonance imaging (PET/MRI) is based on tissue type segmentation. Due to lack of MR signal in cortical bone and the varying signal of spongeous bone, standard whole-body segmentation-based MRAC ignores the higher attenuation of bone compared to the one of soft tissue (MRACnobone). The authors aim to quantify and reduce the bias introduced by MRACnobone in the standard uptake value (SUV) of spinal and pelvic lesions in 20 PET/MRI examinations with [18F]NaF. METHODS The authors reconstructed 20 PET/MR [18F]NaF patient data sets acquired with a Philips Ingenuity TF PET/MRI. The PET raw data were reconstructed with two different attenuation images. First, the authors used the vendor-provided MRAC algorithm that ignores the higher attenuation of bone to reconstruct PETnobone. Second, the authors used a threshold-based algorithm developed in their group to automatically segment bone structures in the [18F]NaF PET images. Subsequently, an attenuation coefficient of 0.11 cm(-1) was assigned to the segmented bone regions in the MRI-based attenuation image (MRACbone) which was used to reconstruct PETbone. The automatic bone segmentation algorithm was validated in six PET/CT [18F]NaF examinations. Relative SUVmean and SUVmax differences between PETbone and PETnobone of 8 pelvic and 41 spinal lesions, and of other regions such as lung, liver, and bladder, were calculated. By varying the assigned bone attenuation coefficient from 0.11 to 0.13 cm(-1), the authors investigated its influence on the reconstructed SUVs of the lesions. RESULTS The comparison of [18F]NaF-based and CT-based bone segmentation in the six PET/CT patients showed a Dice similarity of 0.7 with a true positive rate of 0.72 and a false discovery rate of 0.33. The [18F]NaF-based bone segmentation worked well in the pelvis and spine. However, it showed artifacts in the skull and in the extremities. The analysis of the 20 [18F]NaF PET/MRI examinations revealed relative SUVmax differences between PETnobone and PETbone of (-8.8%±2.7%, p=0.01) and (-8.1%±1.9%, p=2.4×10(-8)) in pelvic and spinal lesions, respectively. A maximum SUVmax underestimation of -13.7% was found in lesion in the third cervical spine. The averaged SUVmean differences in volumes of interests in lung, liver, and bladder were below 3%. The average SUVmax differences in pelvic and spinal lesions increased from -9% to -18% and -8% to -17%, respectively, when increasing the assigned bone attenuation coefficient from 0.11 to 0.13 cm(-1). CONCLUSIONS The developed automatic [18F]NaF PET-based bone segmentation allows to include higher bone attenuation in whole-body MRAC and thus improves quantification accuracy for pelvic and spinal lesions in [18F]NaF PET/MRI examinations. In nonbone structures (e.g., lung, liver, and bladder), MRACnobone yields clinically acceptable accuracy.

Preliminary evaluation of the MLAA algorithm with the Philips Ingenuity PET/MR.

Combined PET/MR is a promising tool for simultaneous investigation of soft tissue morphology and function. However, contrary to CT, MR images do not provide information on photon attenuation in tissue. In the currently available systems issue is solved by synthesizing attenuation maps from MR images using segmentation algorithms. This approach has been shown to provide reason-able results in most cases. However, sporadically occurring segmentation errors can cause serious problems. Recently, algorithms for simultaneous estimation of attenuation and tracer distribution (MLAA) have been introduced. So far, validity of MLAA has mainly been demonstrated in simulated data. We have integrated the MLAA algorithm [2] into the THOR reconstruction [1]. An evaluation of MLAA was performed using both phantom and patient data acquired with the Ingenuity PET/MR. Phantom data were acquired using a whole body phantom with three cylindrical inserts filled with different substances (plastic, air, glycerol). MLAA-estimated mu-maps of the phantom were compared to the mu-maps resulting from transmission measurements with an ECAT HR+ scanner. We also performed a first qualitative evaluation of the attenuation maps obtained in patient studies. Evaluation of the phantom study showed good concordance between measured and estimated attenuation coefficients for all types of substances used in the phantom. Evaluation of patient data showed some substantial improvements of the MLAA attenuation maps compared to the segmented MR-based attenuation maps. Preliminary results show that for the Philips Ingenuity PET/MR scanner the MLAA algorithm allows to obtain attenuation maps which outperform the MR based maps in several aspects. However, a more detailed analysis is still required to address the question of possible cross-talks in regions with high activity. Additionally, MLAA algorithm substantially increases computational burden leading to long processing times, which makes it currently impractical for clinical application.

Photon vs. proton radiochemotherapy: Effects on brain tissue volume and perfusion

BACKGROUND AND PURPOSE To compare the structural and hemodynamic changes of healthy brain tissue in the cerebral hemisphere contralateral to the tumor following photon and proton radiochemotherapy. MATERIALS AND METHODS Sixty-seven patients (54.9 ±14.0 years) diagnosed with glioblastoma undergoing adjuvant photon (n = 47) or proton (n = 19) radiochemotherapy with temozolomide after tumor resection underwent T1-weighted and arterial spin labeling MRI. Changes in volume and perfusion before and 3 to 6 months after were compared between therapies. RESULTS A decrease in gray matter (GM) (-2.2%, P<0.001) and white matter (WM) (-1.2%, P<0.001) volume was observed in photon-therapy patients compared to the pre-radiotherapy baseline. In contrast, for the proton-therapy group, no significant differences in GM (0.3%, P = 0.64) or WM (-0.4%, P = 0.58) volume were observed. GM volume decreased with 0.9% per 10 Gy dose increase (P<0.001) and differed between the radiation modalities (P<0.001). Perfusion decreased in photon-therapy patients (-10.1%, P = 0.002), whereas the decrease in proton-therapy patients, while comparable in magnitude, did not reach statistical significance (-9.1%, P = 0.12). There was no correlation between perfusion decrease and either dose (P = 0.64) or radiation modality (P = 0.94). CONCLUSIONS Our results show that the tissue volume decrease depends on radiation dose delivered to the healthy hemisphere and differs between treatment modalities. In contrast, the decrease in perfusion was comparable for both irradiation modalities. We conclude that proton therapy may reduce brain-volume loss when compared to photon therapy.