Respiratory and cardiac motion correction in positron emission tomography using elastic motion approach for simultaneous abdomen and thorax positron emission tomography-magnetic resonance imaging.

Background: Cardiac and respiratory motions in clinical positron emission tomography (PET) are a major contributor to inaccurate PET quantification and lesion characterisation. In this study, an elastic motion-correction (eMOCO) technique based on mass preservation optical flow is adapted and investigated for positron emission tomography-magnetic resonance imaging (PET-MRI) applications. Methods: The eMOCO technique was investigated in a motion management QA phantom and in twenty-four patients who underwent PET-MRI for dedicated liver imaging and nine patients for cardiac PET-MRI evaluation. Acquired data were reconstructed with eMOCO and gated motion correction techniques at cardiac, respiratory and dual gating modes, and compared to static images. Standardized uptake value (SUV), signal-to-noise ratio (SNR) of lesion activities from each gating mode and correction technique were measured and their means/standard deviation (SD) were compared using 2-ways ANOVA analysis and post-hoc Tukey's test. Results: Lesions' SNR are highly recovered from phantom and patient studies. The SD of the SUV resulted from the eMOCO technique was statistically significantly less (P<0.01) than the SD resulted from conventional gated and static SUVs at the liver, lung and heart. Conclusions: The eMOCO technique was successfully implemented in PET-MRI in a clinical setting and produced the lowest SD compared to gated and static images, and hence provided the least noisy PET images. Therefore, the eMOCO technique can potentially be used on PET-MRI for improved respiratory and cardiac motion correction.

Impact of PET scanner non-linearity on the estimation of hypoxic fraction in cervical cancer patients.

BACKGROUND: Tumor hypoxia is defined as a low oxygen level in tissue and is associated with poor clinical outcome after chemo-/radiotherapy and surgery in many solid tumor types. Positron Emission Tomography (PET) imaging provides a non-invasive means of measuring local variations in the uptake of hypoxia-targeted agents (e.g. FAZA or FMISO). Accurate quantification of uptake is critically dependent on the PET scanner's linear count rate performance. In the context of cervix cancer, high PET agent accumulation in the bladder, low uptake in the tumor, and their relative proximity makes an accurate quantification of the tumor's hypoxic fraction challenging. The purpose of this study was to estimate the impact of PET scanner non-linearity on PET-based estimation of hypoxic fraction. MATERIAL AND METHODS: The impact of PET scanner non-linearity effect was assessed with a NEMA body phantom, using the cylinder as the "bladder-mimicking" compartment and the water filled background as a surrogate region for the tumor. A simple model of the non-linearity effect was then applied to a set of patient-derived FAZA-PET scans (N = 38) to estimate the impact of the non-linearity on the calculated hypoxic fraction (HF) for each patient. RESULTS: The NEMA body phantom measurements revealed a substantial overestimate of activity outside the injected "bladder mimicking" cylinder compartment. This uptake resulted in an overestimate in activity between 1.9 and 0.3 kBq/cc corresponding to distances from 1.0 - 7.0 cm from the cylinder. In the patient-derived PET images, the bladder-to-tumor distance ranged between 1.0 and 3.0 cm. For the 38 patients analyzed, the HF was demonstrated to decrease by 1.1-75.0 % [median 27.2 %] depending on distance and relative uptake levels. Additionally, the magnitude of the effect of the non-linearity was found to depend on the pre-scanning hydration protocol employed (p = 0.0065). CONCLUSION: Hypoxia imaging of tumors of the cervix is challenging due to patient specific activity accumulation in the bladder and the non-linear response of PET scanner performance. This can result in a substantial overestimate of the calculated hypoxic fraction in cervical tumors. Additional effort needs to be invested to improve the linearity of PET scanners in anatomical regions proximal to the bladder.

Phantom Validation of a Conservation of Activity-Based Partial Volume Correction Method for Arterial Input Function in Dynamic PET Imaging.

Dynamic PET (dPET) imaging can be utilized to perform kinetic modelling of various physiologic processes, which are exploited by the constantly expanding range of targeted radiopharmaceuticals. To date, dPET remains primarily in the research realm due to a number of technical challenges, not least of which is addressing partial volume effects (PVE) in the input function. We propose a series of equations for the correction of PVE in the input function and present the results of a validation study, based on a purpose built phantom. 18F-dPET experiments were performed using the phantom on a set of flow tubes representing large arteries, such as the aorta (1" 2.54 cm ID), down to smaller vessels, such as the iliac arteries and veins (1/4" 0.635 cm ID). When applied to the dPET experimental images, the PVE correction equations were able to successfully correct the image-derived input functions by as much as 59 ± 35% in the presence of background, which resulted in image-derived area under the curve (AUC) values within 8 ± 9% of ground truth AUC. The peak heights were similarly well corrected to within 9 ± 10% of the scaled DCE-CT curves. The same equations were then successfully applied to correct patient input functions in the aorta and internal iliac artery/vein. These straightforward algorithms can be applied to dPET images from any PET-CT scanner to restore the input function back to a more clinically representative value, without the need for high-end Time of Flight systems or Point Spread Function correction algorithms.

Noise-Based Image Harmonization Significantly Increases Repeatability and Reproducibility of Radiomics Features in PET Images: A Phantom Study.

For multicenter clinical studies, characterizing the robustness of image-derived radiomics features is essential. Features calculated on PET images have been shown to be very sensitive to image noise. The purpose of this work was to investigate the efficacy of a relatively simple harmonization strategy on feature robustness and agreement. A purpose-built texture pattern phantom was scanned on 10 different PET scanners in 7 institutions with various different image acquisition and reconstruction protocols. An image harmonization technique based on equalizing a contrast-to-noise ratio was employed to generate a "harmonized" alongside a "standard" dataset for a reproducibility study. In addition, a repeatability study was performed with images from a single PET scanner of variable image noise, varying the binning time of the reconstruction. Feature agreement was measured using the intraclass correlation coefficient (ICC). In the repeatability study, 81/93 features had a lower ICC on the images with the highest image noise as compared to the images with the lowest image noise. Using the harmonized dataset significantly improved the feature agreement for five of the six investigated feature classes over the standard dataset. For three feature classes, high feature agreement corresponded with higher sensitivity to the different patterns, suggesting a way to select suitable features for predictive models.

A method for patient dose reduction in dynamic contrast enhanced CT study.

PURPOSE: In dynamic contrast enhanced CT (DCE-CT) study, prolonged CT scanning with high temporal resolution is required to give accurate and precise estimates of kinetic parameters. However, such scanning protocol could lead to substantial radiation dose to the patient. A novel method is proposed to reduce radiation dose to patient, while maintaining high accuracy for kinetic parameter estimates in DCE-CT study. METHODS: The method is based on a previous investigation that the arterial impulse response (AIR) in DCE-CT study can be predicted using a population-based scheme. In the proposed method, DCE-CT scanning is performed with relatively low temporal resolution, hence, giving rise to reduction in patient dose. A novel method is proposed to estimate the arterial input function (AIF) based on the coarsely sampled AIF. By using the estimated AIF in the tracer kinetic analysis of the coarsely sampled DCE-CT study, the calculated kinetic parameters are able to achieve a high degree of accuracy. The method was tested on a DCE-CT data set of 48 patients with cervical cancer scanned at high temporal resolution. A random cohort of 34 patients was chosen to construct the orthonormal bases of the AIRs via singular value decomposition method. The determined set of orthonormal bases was used to fit the AIFs in the second cohort (14 patients) at varying levels of down sampling. For each dataset in the second cohort, the estimated AIF was used for kinetic analyses of the modified Tofts and adiabatic tissue homogeneity models for each of the down-sampling schemes between intervals from 2 to 15 s. The results were compared with analyses done with the "raw" down-sampled AIF. RESULTS: In the first group of 34 patients, there were 11 orthonormal bases identified to describe the AIRs. The AIFs in the second group were estimated in high accuracy based on the 11 orthonormal bases established in the first group along with down-sampled AIFs. Using the 11 orthonormal bases, the estimated AIFs for the second group were found to have an averaged maximal percentage error of 3.4% ± 7.5% in all sampling schemes up to 15 s. The results of kinetic analysis with the proposed method compared with down sampling alone showed that the proposed method is superior in maintaining the accuracy in volume transfer constant (K(trans) ) after 9 s down-sampling interval, blood volume (v(b) ) for almost all down-sampling intervals, and blood flow (F) after 11 s down-sampling interval. The preliminary results suggested that the proposed method is able to support scanning intervals of 10-15 s at a cost of 6.2%-10.0% loss in accuracy of K(trans) and 10.9%-19.4% in v(b), and the scanning intervals of 12-15 s at a cost of 9.7%-14.6% for F in DEC-CT studies for patients with cervix cancer. CONCLUSIONS: The proposed method of AIF estimation allows low scanning frequency in DCE-CT study to reduce radiation dose to patient, while maintaining relatively high accuracy in the kinetic parameter estimates. The initial results suggested that the method is applicable for DCE-CT studies for patients with cervical cancer.

Simulated dose painting of hypoxic sub-volumes in pancreatic cancer stereotactic body radiotherapy.

Dose painting of hypoxic tumour sub-volumes using positron-emission tomography (PET) has been shown to improve tumour controlin silicoin several sites, predominantly head and neck and lung cancers. Pancreatic cancer presents a more stringent challenge, given its proximity to critical gastro-intestinal organs-at-risk (OARs), anatomic motion, and impediments to reliable PET hypoxia quantification. A radiobiological model was developed to estimate clonogen survival fraction (SF), using18F-fluoroazomycin arabinoside PET (FAZA PET) images from ten patients with unresectable pancreatic ductal adenocarcinoma to quantify oxygen enhancement effects. For each patient, four simulated five-fraction stereotactic body radiotherapy (SBRT) plans were generated: (1) a standard SBRT plan aiming to cover the planning target volume with 40 Gy, (2) dose painting plans delivering escalated doses to a maximum of three FAZA-avid hypoxic sub-volumes, (3) dose painting plans with simulated spacer separating the duodenum and pancreatic head, and (4), plans with integrated boosts to geometric contractions of the gross tumour volume (GTV). All plans saturated at least one OAR dose limit. SF was calculated for each plan and sensitivity of SF to simulated hypoxia quantification errors was evaluated. Dose painting resulted in a 55% reduction in SF as compared to standard SBRT; 78% with spacer. Integrated boosts to hypoxia-blind geometric contractions resulted in a 41% reduction in SF. The reduction in SF for dose-painting plans persisted for all hypoxia quantification parameters studied, including registration and rigid motion errors that resulted in shifts and rotations of the GTV and hypoxic sub-volumes by as much as 1 cm and 10 degrees. Although proximity to OARs ultimately limited dose escalation, with estimated SFs (∼10-5) well above levels required to completely ablate a ∼10 cm3tumour, dose painting robustly reduced clonogen survival when accounting for expected treatment and imaging uncertainties and thus, may improve local response and associated morbidity.

Comparison of quantitative parameters in cervix cancer measured by dynamic contrast-enhanced MRI and CT.

Cervical tumors of 38 cervix cancer patients were scanned by T(1)-weighted dynamic contrast enhanced (DCE) MRI and then by DCE-CT on the same day. Gadodiamide and iohexol were respectively used as the low-molecular-weight contrast agent in DCE-MRI and DCE-CT. Under an extended Tofts model, DCE-MRI data were analyzed using either individual arterial input functions estimated by a multiple reference tissue method or a population arterial input function by Parker et al., whereas DCE-CT data were analyzed using the arterial input function directly measured from the external iliac arteries. The derived quantitative parameters of cervical tumors were compared between DCE-MRI and DCE-CT. When using the individual multiple reference tissue method arterial input functions to analyze the DCE-MRI data, the correlation coefficients between DCE-MRI- and DCE-CT-derived parameters were, respectively, back-flux rate constant (r = 0.80), extravascular extracellular fractional volume (r = 0.73), contrast agent transfer rate (r = 0.62), and blood plasma volume (r = 0.32); when using the Parker population arterial input function, the correlation coefficients were back-flux rate constant (r = 0.79), extravascular extracellular fractional volume (r = 0.77), contrast agent transfer rate (r = 0.63), and blood plasma volume (r = 0.58). Tumor parametric maps derived by DCE-MRI and DCE-CT had very similar morphologies. However, the means of most derived quantitative parameters were significantly different between the two imaging methods. Close correlation of quantitative parameters derived from two independent imaging modalities suggests both are measuring similar tumor physiologic variables.

Robust texture features for response monitoring of glioblastoma multiforme on T1-weighted and T2-FLAIR MR images: a preliminary investigation in terms of identification and segmentation.

PURPOSE: Image texture has recently attracted much attention in providing quantitative features that are unique to various different tissue types, in particular, in MR images of the brain. Such image features may be useful for tumor response quantification. As a first step, one needs to establish if these features are sensitive to different tissues of clinical relevance. Here, a novel method of texture analysis based on the Hartley transform has been investigated and applied to MR images of glioblastoma multiforme (GBM). METHODS: Contrast-enhanced T1-weighted gradient-echo and T2-FLAIR spin-echo MR images of 27 GBM patients acquired prior to radiation therapy were available for analysis. Before computing texture features on these images, a novel image transformation was employed in the form of a power map computed from the localized Hartley transform of the image. Haralick statistical texture features were then computed based on the power map. This method was compared to the standard approach of obtaining texture features directly from the image. Twelve different features were computed on different resolution levels. On a regional resolution level, image texture features were identified that are able to correctly classify entire regions within T1-weighted and T2-FLAIR brain MR images of GBM patients into abnormal (containing contrast-enhancing GBM tumor) and brain tissue. Various metrics [area under the ROC curve (AUC), maximum accuracy, and Canberra distance] have been computed to quantify the usefulness of these features. On a local resolution level, it was investigated which of these features are able to provide a voxel-by-voxel enhancement that could be used for assisting the segmentation of the gross tumor volume on T1 images. The "gold standard" for this analysis was a gross tumor volume corresponding to the contrast-enhancing lesion visualized on T1-weighted images as segmented by a radiation oncologist. RESULTS: The Sum-mean and Variance features demonstrated the best performance overall. For the T1-weighted images, the identification performance of Sum-mean and Variance features computed from the power map was higher (AUC = 0.9959 and AUC = 0.9918, respectively) and with higher Canberra distances as compared to features computed directly from the images (AUC = 0.8930 and AUC = 0.9163, respectively). These results in T2-FLAIR images were even superior. The features computed from the power map showed an unequivocal identification (AUC = 1) with higher Canberra distances, whereas the performance of the features from the original images was slightly lower (AUC = 0.9739 and AUC = 0.9904, respectively). The same features computed on the power map of the T1-weighted images also provided superior enhancement in individual tumor voxels as compared to the features computed on the original images. CONCLUSIONS: The Sum-mean and Variance features are both useful for identifying and segmenting GBM tumors on localized Hartley transformed MR images.

4D-CT Attenuation Correction in Respiratory-Gated PET for Hypoxia Imaging: Is It Really Beneficial?

Previous literature has shown that 4D respiratory-gated positron emission tomography (PET) is beneficial for quantitative analysis and defining targets for boosting therapy. However the case for addition of a phase-matched 4D-computed tomography (CT) for attenuation correction (AC) is less clear. We seek to validate the use of 4D-CT for AC and investigate the impact of motion correction for low signal-to-background PET imaging of hypoxia using radiotracers such as FAZA and FMISO. A new insert for the Modus Medicals' QUASAR™ Programmable Respiratory Motion Phantom was developed in which a 3D-printed sphere was placed within the "lung" compartment while an additional compartment is added to simulate muscle/blood compartment required for hypoxia quantification. Experiments are performed at 4:1 or 2:1 signal-to-background ratio consistent with clinical FAZA and FMISO imaging. Motion blur was significant in terms of SUVmax, mean, and peak for motion ≥1 cm and could be significantly reduced (from 20% to 8% at 2-cm motion) for all 4D-PET-gated reconstructions. The effect of attenuation method on precision was significant (σ2 hCT-AC = 5.5%/4.7%/2.7% vs σ2 4D-CT-AC = 0.5%/0.6%/0.7% [max%/peak%/mean% variance]). The simulated hypoxic fraction also significantly decreased under conditions of 2-cm amplitude motion from 55% to 20% and was almost fully recovered (HF = 0.52 for phase-matched 4D-CT) using gated PET. 4D-gated PET is valuable under conditions of low radiotracer uptake found in hypoxia imaging. This work demonstrates the importance of using 4D-CT for AC when performing gated PET based on its significantly improved precision over helical CT.

Quantitative assessment of dynamic 18F-flumethycholine PET and dynamic contrast enhanced MRI in high risk prostate cancer.

OBJECTIVE:: To describe dynamic 18F-flumethycholine PET (dPET) and dynamic contrast enhancement MR (DCE MR) parameters in localized high-risk prostate cancer (PCa), and determine whether these differ from normal prostate. Furthermore, to determine whether a correlation exists between dPET and DCE MR parameters. METHODS:: 41 consenting patients who underwent prostate DCE MR and dPET were included in this institutionally approved study. Intraprostatic lesions on MR were assigned a PI-RADS v2 score, and focal lesions on PET were documented. All lesions were correlated with pathology. Quantitative and semi-quantitative DCE MR and two-tissue compartmental model dPET parameters were determined and tumor-to-normal gland ratios (T/N) for these parameters were calculated. Finally, dPET and DCE MR correlation was estimated using Spearman correlation coefficients. RESULTS:: There were 46 malignant lesions per standard of reference. On dPET, peripheral zone (PZ) tumors had higher K1 (p < 0.001), and a T/N ratio ≥2 was significant (p < 0.001). On DCE MR, the parameters in, kep, Ktrans and quantitative iAUC were higher for PZ and non-PZ tumors than corresponding normal tissue (p < 0.001); for PZ tumors, a T/N ratio ≥ 1.5 for Ktrans and pei was significant (p = 0.0019 and 0.0026, respectively). Moderate Spearman correlation (0.40 < ρ < 0.59) was found between dPET K1 and DCE MR Ktrans and pei. CONCLUSION:: In patients with high-risk PCa, quantitative dPET and DCE-MR parameters in primary tumors differ from normal tissue. Only moderate correlation exists between K1 (dPET) and Ktrans and pei (DCE MR). The incremental value of any of these parameters to PI-RADS v2 warrants further investigation. ADVANCES IN KNOWLEDGE:: Unique quantitative and semi-quantitative FCH PET/MR parameters in PCa differ from normal gland, and should be further investigated to determine their potential contribution to PI-RADS v2 in the detection of clinically significant PCa.

Development of a Collaboration Model between Two Cancer Centres to Maintain Patient Access to Radiation Therapy during the Replacement of a Sole CT Simulator at a Regional Cancer Centre.

INTRODUCTION: Replacement of a sole computed tomography (CT) simulator at a Regional Cancer Centre risks interruption of patient access to radiation therapy clinical services. This study reports a collaboration model between two cancer centres to maintain patient access to radiation therapy during the replacement period. METHODS: Representatives from each cancer centre collaborated to plan and facilitate offsite CT simulation. Activities required were identified and included process coordination, patient consent, patient registration, requisitions, appointment bookings, immobilization equipment, staffing strategy, clinical practice protocols, data transfer, and cost recovery. The logistics of each activity were planned and mapped, with roles identified to perform each activity. During the 2-week replacement duration, from April 30 to May 11, 2018, patients consulted for radiotherapy were offered offsite CT simulation. RESULTS: A detailed process was developed to outline the flow of activities for successful coordination of offsite CT simulations. A total of 14 patients consented to radiation treatment during the CT simulator replacement downtime, of which 8 patients agreed to offsite CT simulation. A total of 11 body regions were simulated for the 8 patients. CT images acquired offsite were electronically transferred to the primary cancer centre to proceed with treatment planning and delivery. DISCUSSION: A collaboration model between two cancer centres was successfully developed and implemented to maintain patient access to radiation therapy during the replacement of a sole CT simulator at a regional cancer centre. CONCLUSION: This strategy and process developed could be valuable for future major equipment upgrades/replacements at other centres.

A dual modality phantom for cone beam CT and ultrasound image fusion in prostate implant.

In transrectal ultrasound (TRUS) guided prostate seed brachytherapy, TRUS provides good delineation of the prostate while x-ray imaging, e.g., C-arm, gives excellent contrast for seed localization. With the recent availability of cone beam CT (CBCT) technology, the combination of the two imaging modalities may provide an ideal system for intraoperative dosimetric feedback during implantation. A dual modality phantom made of acrylic and copper wire was designed to measure the accuracy and precision of image coregistration between a C-arm based CBCT and 3D TRUS. The phantom was scanned with TRUS and CBCT under the same setup condition. Successive parallel transverse ultrasound (US) images were acquired through manual stepping of the US probe across the phantom at an increment of 1 mm over 7.5 cm. The CBCT imaging was done with three reconstructed slice thicknesses (0.4, 0.8, and 1.6 mm) as well as at three different tilt angles (0 degrees, 15 degrees, 30 degrees), and the coregistration between CBCT and US images was done using the Variseed system based on four fiducial markers. Fiducial localization error (FLE), fiducial registration error (FRE), and target registration error (TRE) were calculated for all registered image sets. Results showed that FLE were typically less than 0.4 mm, FRE were less than 0.5 mm, and TRE were typically less than 1 mm within the range of operation for prostate implant (i.e., < 6 cm to surface of US probe). An analysis of variance test showed no significant difference in TRE for the CBCT-US fusion among the three slice thicknesses (p = 0.37). As a comparison, the experiment was repeated with a US-conventional CT scanner combination. No significant difference in TRE was noted between the US-conventional CT fusion and that for all three CBCT image slice thicknesses (p = 0.21). CBCT imaging was also performed at three different C-arm tilt angles of 0 degrees, 15 degrees and 30 degrees and reconstructed at a slice thickness of 0.8 mm. There is no significant difference in TRE between 0 degrees and 15 degrees (p = 0.191) as well as between 0 degrees and 30 degrees (p = 0.275), which suggests that the C-arm may be tilted intraoperatively to acquire CBCT images without compromising the quality of image fusion. The results conclude a high degree of accuracy and precision for the CBCT-TRUS fusion, which could be useful toward achieving real time intraoperative dosimetry in prostate brachytherapy.

Loose seeds vs. stranded seeds: a comparison of critical organ dosimetry and acute toxicity in (125)I permanent implant for low-risk prostate cancer.

PURPOSE: To compare the critical organ dosimetry and toxicity of loose seeds (LS) with stranded seeds (SS) in (125)I permanent implant for low-risk prostate cancer. METHODS AND MATERIALS: Two cohorts of 20 patients each were treated in Institutional Review Board-approved protocols designed to assess prostate edema and seed stability using MR-CT fusion on Days 0, 7, and 30 after permanent implant. (125)I LS were used for one cohort and (125)I SS for the other. Rectal wall dosimetry was compared for the two cohorts using RV100 and RD1cc and urethral dosimetry using UD5, UD30, and UV150. Statistical comparisons were performed using unpaired Student's t test. RESULTS: At each time point (Days 0, 7, and 30), both the mean RD1 cc (SS: 123.1, 139.7, and 156.1 Gy vs. LS: 90.2, 104, and 129.4 Gy, respectively) and the mean RV100 (SS: 0.63, 1.0, and 1.4 cc vs. LS: 0.2, 0.4, and 0.73 cc, respectively) were significantly higher for strands (all p-values<0.01). Only 1 patient developed radiotherapy oncology group (RTOG) Grade 1 acute rectal toxicity in the loose seed cohort, whereas 3 patients had Grade 1 and 1 patient had Grade 2 toxicity with strands. The mean percentage increase of UD5 (7.7% LS vs. 24.6% SS; p=0.004) and UD30 (5% LS vs. 15.9% SS; p=0.02) from preplan to Day 30 was higher for strands. The increase in UV150 from baseline to Day 30 was significantly higher for strands (0.2 vs. 0.06 cc; p=0.01). Urinary toxicity was similar in both cohorts. CONCLUSIONS: SS resulted in higher dose to urethra and rectal wall compared with LS on postimplant dosimetry. A trend toward higher acute rectal toxicity rate was observed for SS.

Outcomes of Peer Review for Radiotherapy Treatment Plans With Palliative Intent.

PURPOSE: Peer review of a proposed treatment plan is increasingly recognized as an important quality activity in radiation medicine. Although peer review has been emphasized in the curative setting, applying peer review for treatment plans that have palliative intent is receiving increased attention. This study reports peer review outcomes for a regional cancer center that applied routine interprofessional peer review as a standard practice for palliative radiotherapy. METHODS AND MATERIALS: Peer review outcomes for palliative radiotherapy plans were recorded prospectively for patients who began radiotherapy between October 1, 2015, and September 30, 2017. Recommended and implemented changes were recorded. The content of detailed discussions was recorded to gain insight into the complexities of palliative treatment plans considered during peer review. RESULTS: Peer review outcomes were reviewed for 1,413 treatment plans with palliative intent. The proportions of detailed discussions and changes recommended were found to be 139 (9.8%) and 29 (2.1%), respectively. The content of detailed discussions and changes recommended was categorized. Major changes represented 75.9% of recommended changes, of which 84.2% were implemented clinically. CONCLUSION: Many complexities exist that are specific to palliative radiotherapy. Interprofessional peer review provides a forum for these complexities to be openly discussed and is an important activity to optimize the quality of care for patients with treatment plans that have palliative intent.

Inter-operator variability in compartmental kinetic analysis of 18F-fluoromisonidazole dynamic PET.

PURPOSE: To assess the inter-operator variability in compartment analysis (CA) of dynamic-FMISO (dyn-FMISO) PET. METHODS: Study-I: Five investigators conducted CA for 23 NSCLC dyn-FMISO tumor time-activity-curves. Study-II: Four operators performed CA for four NSCLC dyn-FMISO datasets. Repeatability of Kinetic-Rate-Constants (KRCs) was assessed. RESULTS: Study-I: Strong correlation (ICC > 0.9) and interchangeable results among operators existed for all KRCs. Study-II: Up to 103% variability in tumor segmentation, and weaker ICC in KRCs (ICC-VB = 0.53; ICC-K1 = 0.91; ICC-K1/k2 = 0.25; ICC-k3 = 0.32; ICC-Ki = 0.54) existed. All KRCs were repeatable among the different operators. CONCLUSIONS: Inter-operator variability in CA of dyn-FMISO was shown to be within statistical errors.

Measurement of Tumor Hypoxia in Patients With Locally Advanced Cervical Cancer Using Positron Emission Tomography with 18F-Fluoroazomyin Arabinoside.

PURPOSE: To assess cervical tumor hypoxia using the hypoxia tracer 18F-fluoroazomycin arabinoside (18F-FAZA) and compare different reference tissues and thresholds for quantifying tumor hypoxia. METHODS AND MATERIALS: Twenty-seven patients with cervical cancer were studied prospectively by positron emission tomography (PET) imaging with 18F-FAZA before starting standard chemoradiation. The hypoxic volume was defined as all voxels within a tumor (T) with standardized uptake values (SUVs) greater than 3 standard deviations from the mean gluteus maximus muscle SUV value (M) or SUVs greater than 1 to 1.4 times the mean SUV value of the left ventricle, a blood (B) surrogate. The hypoxic fraction was defined as the ratio of the number of hypoxic voxels to the total number of tumor voxels. RESULTS: A 18F-FAZA-PET hypoxic volume could be identified in the majority of cervical tumors (89% when using T/M or T/B > 1.2 as threshold) on the 2-hour static scan. The hypoxic fraction ranged from 0% to 99% (median 31%) when defined using the T/M threshold and from 0% to 78% (median 32%) with the T/B > 1.2 threshold. Hypoxic volumes derived from the different thresholds were highly correlated (Spearman's correlation coefficient ρ between T/M and T/B > 1-1.4 were 0.82-0.91), as were hypoxic fractions (0.75-0.85). Compartmental analysis of the dynamic scans showed k3, the FAZA accumulation constant, to be strongly correlated with hypoxic fraction defined using the T/M (Spearman's ρ=0.72) and T/B > 1.2 thresholds (0.76). CONCLUSIONS: Hypoxia was detected in the majority of cervical tumors on 18F-FAZA-PET imaging. The extent of hypoxia varied markedly between tumors but not significantly with different reference tissues/thresholds.

PSA kinetics and PSA bounce following permanent seed prostate brachytherapy.

PURPOSE: To report the incidence, timing, and magnitude of the benign prostate-specific antigen (PSA) bounce after 125I prostate brachytherapy and correlate the bounce with clinical and/or dosimetric factors. METHODS AND MATERIALS: From March 1999 to August 2003, a total of 292 men received 125I prostate brachytherapy without androgen deprivation or supplemental beam radiotherapy and have PSA follow-up >30 months. Implants were preplanned using transrectal ultrasound (TRUS) and performed under transrectal ultrasound/fluoroscopy guidance using preloaded needles. A PSA bounce is defined as an increase >or=0.2 ng/ml with spontaneous return to prebounce level or lower. RESULTS: Resolved PSA bounces were seen in 40% of men with follow-up >30 months. Median onset was 15 months, and median magnitude was 0.76 ng/ml. Magnitude >2 ng/ml was seen in 15%. The only clinical or dosimetric factor predictive of bounce in multivariate analysis was younger age. Median time to increasing PSA level indicative of failure was 30 months. CONCLUSIONS: Benign PSA bounces are common after 125I prostate brachytherapy, especially in younger men. An increase >2 ng/ml above the nadir was seen in 15%. Magnitude of increase does not distinguish bounce from failure. Time to the start of the PSA increase can be helpful, but is not absolute. The PSA bounce does not predict subsequent failure. Caution is advised in interpreting an early increasing PSA level in the first 30 months after 125I brachytherapy in favorable-risk patients.

The nature and extent of urinary morbidity in relation to prostate brachytherapy urethral dosimetry.

PURPOSE: This study investigates whether the location and dose of urethral radiation received during transperineal interstitial permanent prostate brachytherapy determine the degree and type of urinary symptoms experienced subsequently. METHODS AND MATERIALS: Data from a prospectively acquired database of 219 men treated with transperineal interstitial permanent prostate brachytherapy using (125)I (prescribed dose 145Gy) between May 2001 and June 2003 were reviewed. To assess the effect of regional urethral dosimetry, the prostate was divided into equal thirds (proximal, mid, and apical) with doses beyond this considered distal. Mean and peak doses for each region were correlated with total International Prostate Symptom Score (IPSS) and the irritative and obstructive components of the score. IPSS values at 1 month postimplant, time to resolution of IPSS, and the need for catheterization were used as outcome variables and analyzed with respect to dose using logistic and linear regression. RESULTS: Peak and average doses with standard deviations to the proximal urethra were 168 (24) and 147 (24)Gy, mid prostatic urethra 192 (24) and 181 (21)Gy, and apical urethra 201 (28) and 192 (26)Gy. Catheterization was required for 28 men and was predicted by larger pretreatment transrectal ultrasound (TRUS) volume (OR 1.06 per unit change; 95% CI 1.03-1.10; p<0.001) and lower UV(150) (OR 0.30; 95% CI 0.13-0.68; p=0.004) in multivariate analysis. Greater IPSS at baseline (p<0.001) and preoperative TRUS volume (p=0.012) but conversely smaller D(30) doses (p=0.003) were predictive of IPSS outcomes at 1 month. IPSS returned to within two points of baseline for 72.2% of men by 1 year and 83.3% by 24 months. This was predicted by higher IPSS at baseline (OR 6.0; 95% CI 2.72-13.22; p<0.001), higher D(30) (OR 1.17; 95% CI 1.01-1.36; p=0.031), and lower V(100) (OR 0.39; 95% CI 0.22-0.70; p=0.002). Prostatic urethral segmental dosimetry failed to predict the need for catheterization, the nature of the urinary symptoms, or their time to resolution. CONCLUSIONS: Previously identified factors of importance for urinary morbidity such as pretreatment prostate volume and baseline urinary function were reemphasized in this study. Regional urethral dosimetry within contemporary practice does not seem to influence the nature or extent of urinary symptoms after prostate brachytherapy. Consequently, region sparing dosimetric modifications are not warranted to alter symptomatic outcomes.

Impact of tissue transport on PET hypoxia quantification in pancreatic tumours.

BACKGROUND: The clinical impact of hypoxia in solid tumours is indisputable and yet questions about the sensitivity of hypoxia-PET imaging have impeded its uptake into routine clinical practice. Notably, the binding rate of hypoxia-sensitive PET tracers is slow, comparable to the rate of diffusive equilibration in some tissue types, including mucinous and necrotic tissue. This means that tracer uptake on the scale of a PET imaging voxel-large enough to include such tissue and hypoxic cells-can be as much determined by tissue transport properties as it is by hypoxia. Dynamic PET imaging of 20 patients with pancreatic ductal adenocarcinoma was used to assess the impact of transport on surrogate metrics of hypoxia: the tumour-to-blood ratio [TBR(t)] at time t post-tracer injection and the trapping rate k 3 inferred from a two-tissue compartment model. Transport quantities obtained from this model included the vascular influx and efflux rate coefficients, k 1 and k 2, and the distribution volume v d ≡k 1/(k 2+k 3). RESULTS: Correlations between voxel- and whole tumour-scale k 3 and TBR values were weak to modest: the population average of the Pearson correlation coefficients (r) between voxel-scale k 3 and TBR (1 h) [TBR(2 h)] values was 0.10 [0.01] in the 20 patients, while the correlation between tumour-scale k 3 and TBR(2 h) values was 0.58. Using Patlak's formula to correct uptake for the distribution volume, correlations became strong (r=0.80[0.52] and r=0.93, respectively). The distribution volume was substantially below unity for a large fraction of tumours studied, with v d ranging from 0.68 to 1 (population average, 0.85). Surprisingly, k 3 values were strongly correlated with v d in all patients. A model was proposed to explain this in which k 3 is a combination of the hypoxia-sensitive tracer binding rate k b and the rate k eq of equilibration in slow-equilibrating regions occupying a volume fraction 1-v d of the imaged tissue. This model was used to calculate the proposed hypoxia surrogate marker k b. CONCLUSIONS: Hypoxia-sensitive PET tracers are slow to reach diffusive equilibrium in a substantial fraction of pancreatic tumours, confounding quantification of hypoxia using both static (TBR) and dynamic (k 3) PET imaging. TBR is reduced by distribution volume effects and k 3 is enhanced by slow equilibration. We proposed a novel model to quantify tissue transport properties and hypoxia-sensitive tracer binding in order to improve the sensitivity of hypoxia-PET imaging.

Radiation dose to the internal pudendal arteries from permanent-seed prostate brachytherapy as determined by time-of-flight MR angiography.

PURPOSE: To determine the feasibility of time-of-flight magnetic resonance (MR) angiography to visualize the internal pudendal arteries (IPAs) in potent men undergoing permanent-seed prostate brachytherapy and to calculate the radiation dose received by these arteries. METHODS AND MATERIALS: Prostate brachytherapy is performed at the University Health Network/Princess Margaret Hospital by use of transrectal ultrasound (TRUS) preplanning and preloaded needles. All patients received (125)I, with a mean seed activity of 0.32 mCi/seed (0.41 U). Postplan evaluation is performed at 1 month by magnetic resonance-computed tomography fusion. Twenty consecutive potent men had time-of-flight MR angiography as part of their postplan evaluation. RESULTS: The mean V100 was 96.5%, and the mean D90 was171.5 Gy. The IPAs were easily visualized for 18 of the 20 men. The mean peak dose received by the IPA was 17 Gy. The highest peak dose received by any patient was 38.2 Gy, with only 1 other patient receiving a peak dose greater than 30 Gy. Eleven of 18 had a measurable portion of at least 1 IPA that received 10% of the prescribed dose (V10 = 14.5 Gy). Only 2 patients had nonzero values for V25. The distal third of the IPA received the highest dose for 16 of the 18 patients. CONCLUSIONS: The IPAs can be well visualized in the majority of potent men by use of time-of-flight MR angiography 1 month after brachytherapy. The IPAs receive a low but calculable dose from permanent-seed (125)I brachytherapy. Further research is needed to determine if this outcome has any correlation with subsequent potency.