Systematic and random errors of PET-based 90 Y 3D dose quantification.

PURPOSE: The objective was to characterize both systematic and random errors in Positron Emission Tomography (PET)-based 90 Y three-dimensional (3D) dose quantification. METHODS: A modified NEMA-IEC phantom was used to emulate 90 Y-microsphere PET imaging conditions: sphere activity concentrations of 1.6 and 4.8 MBq/cc, sphere-to-background ratios of 4 and 13, and sphere diameters of 13, 17, and 37 mm. PET data were acquired using a GE D690 PET/CT scanner for 300 min on days 0-11. The data were downsampled to 60-5 min for multiple realizations to evaluate the count starvation effect. The image reconstruction algorithm was 3D-OSEM with PSF + TOF modeling; the parameters were optimized for dose-volume histogram (DVH), as a 90 Y 3D dose quantification. 90 Y-PET images were converted to dose maps using the local deposition method, then the sphere DVHs were calculated. The ground truth for the DVH was calculated using convolution method. Dose linearity was evaluated in decaying 90 Y activity (reduced count rate and total count) and decreasing acquisition durations (reduced total count only). Finally, the impacts of the low 32-ppm positron yield on PET-based 3D 90 Y-dose quantification were evaluated; the bias and variability of resulting DVHs were characterized. RESULTS: We observed nonlinear errors that depended on the 90 Y activity (count rate) and not on the total true prompt counts. These nonlinear errors in mean dose underestimated the measured mean dose by> 20% for a measured dose range of 40-230 Gy; although the shapes of the DVH were not altered. Compensation based on empirical models reduced the nonlinearity errors to be within 5% for measured dose range of 40-230 Gy. In contrast, the errors due to nonuniformity introduced by image noise dominated the systematic errors in the DVH and stretched the DVH on both tails. For the 37-mm sphere, the magnitude of errors in D80 increased from -25% to -36% when acquisition duration was decreased from 300 to 10 min. The effect of image noise on DVH was more extensive in smaller spheres; for the 17-mm sphere, the magnitude of errors in D80 increased from -29% to -45% acquisition duration was decreased from 300 to 10 min. For the 37-mm sphere, the errors in D20 increased from +3.5% to only +10.5% when the acquisition duration was decreased from 300 to 10 min; in the 17-mm sphere, the errors in D20 were 6.5% for both 300- and 10-min sphere images. CONCLUSIONS: Count-starved 90 Y-PET data introduce both systematic and random errors. The systematic error increases the apparent nonuniformity of the DVH, while the random error increases the uncertainty in the DVH. The systematic errors were larger than the random errors. Lower count rate of 90 Y-PET also introduces systematic bias, which is scanner specific. The errors of bias-compensated mean tumor dose were <10% when 90 Y-PET scan time was >15 min/bed for tumors >37 mm. Dmedian and Dmean were the most stable dose metrics. An acquisition duration of 30 min is recommended to keep the random errors < 10% for a typical tumor with sphere equivalent diameter >17 mm and average tumor dose >40 Gy.

Effects of image noise, respiratory motion, and motion compensation on 3D activity quantification in count-limited PET images.

The aims of this study were to evaluate the effects of noise, motion blur, and motion compensation using quiescent-period gating (QPG) on the activity concentration (AC) distribution-quantified using the cumulative AC volume histogram (ACVH)-in count-limited studies such as 90Y-PET/CT. An International Electrotechnical Commission phantom filled with low 18F activity was used to simulate clinical 90Y-PET images. PET data were acquired using a GE-D690 when the phantom was static and subject to 1-4 cm periodic 1D motion. The static data were down-sampled into shorter durations to determine the effect of noise on ACVH. Motion-degraded PET data were sorted into multiple gates to assess the effect of motion and QPG on ACVH. Errors in ACVH at AC90 (minimum AC that covers 90% of the volume of interest (VOI)), AC80, and ACmean (average AC in the VOI) were characterized as a function of noise and amplitude before and after QPG. Scan-time reduction increased the apparent non-uniformity of sphere doses and the dispersion of ACVH. These effects were more pronounced in smaller spheres. Noise-related errors in ACVH at AC20 to AC70 were smaller (<15%) compared to the errors between AC80 to AC90 (>15%). The accuracy of ACmean was largely independent of the total count. Motion decreased the observed AC and skewed the ACVH toward lower values; the severity of this effect depended on motion amplitude and tumor diameter. The errors in AC20 to AC80 for the 17 mm sphere were -25% and -55% for motion amplitudes of 2 cm and 4 cm, respectively. With QPG, the errors in AC20 to AC80 of the 17 mm sphere were reduced to -15% for motion amplitudes <4 cm. For spheres with motion amplitude to diameter ratio >0.5, QPG was effective at reducing errors in ACVH despite increases in image non-uniformity due to increased noise. ACVH is believed to be more relevant than mean or maximum AC to calculate tumor control and normal tissue complication probability. However, caution needs to be exercised when using ACVH in post-therapy 90Y imaging because of its susceptibility to image degradation from both image noise and respiratory motion.

New era of radiotherapy: an update in radiation-induced lung disease.

Over the last few decades, advances in radiotherapy (RT) technology have improved delivery of radiation therapy dramatically. Advances in treatment planning with the development of image-guided radiotherapy and in techniques such as proton therapy, allows the radiation therapist to direct high doses of radiation to the tumour. These advancements result in improved local regional control while reducing potentially damaging dosage to surrounding normal tissues. It is important for radiologists to be aware of the radiological findings from these advances in order to differentiate expected radiation-induced lung injury (RILD) from recurrence, infection, and other lung diseases. In order to understand these changes and correlate them with imaging, the radiologist should have access to the radiation therapy treatment plans.

A new parameter for measuring metastatic bone involvement by prostate cancer: the Bone Scan Index.

In this report, we describe a method for quantitative bone scan interpretation (the Bone Scan Index or BSI) in advanced prostate cancer. The BSI estimates the fraction of the skeleton that is involved by tumor, as well as the regional distribution of the metastases in the bones. The purpose of this report is to describe the development and validation of this method in terms of reproducibility and the application of BSI for determining extent of disease and monitoring disease progression. We analyzed 263 bone scans from 90 patients being studied under four protocols at Memorial Sloan-Kettering Cancer Center for progressive, androgen-independent prostate cancer (AIPC), who had bone scans as a part of their work-up. We determined: (a) the intraobserver and interobserver variability of the BSI; (b) the comparison between a change in BSI and prostate-specific antigen (PSA); (c) the regional distribution of bony metastases in early stage D prostate cancer (<3% skeletal involvement); and (d) the rate of growth of bony metastases from prostate cancer. A cube root transformation of the percentage of involvement of the entire skeleton was used to stabilize the variance over the entire span of values (0-60% tumor involvement). The range of interobserver variability between readers was 0.2-0.5 times the cube root of the BSI (69 scans, 18 patients). Intraobserver variability was minimal when the same reader read the same scans after a 2-year interval, showing a correlation coefficient of 0.97 (reader 1) and 0.99 (reader 2), P < 0.001. There was a parallel rise in the BSI and the PSA in 24 patients (105 scans) treated for AIPC with hydrocortisone followed by suramin at PSA relapse (Pearson's moment correlation, 0.71). In a group of 27 patients with limited bone involvement by AIPC (i.e., <3% BSI), the distribution of early metastases was not random within the skeleton but was distributed in the central skeleton in a manner that matched the distribution of the normal adult bone marrow. Also, in a group of 21 patients (62 scans), the change in BSI as a function of time after diagnosis was explored graphically. The progression of bone scan changes in AIPC, from early involvement (<3%) to late involvement, was fitted to a Gompertzian equation. It showed a rapid exponential growth phase, with an estimated tumor doubling time of 43 days when the BSI was 3.3%. The change in BSI rapidly approached a more gradual slope as the percentage of skeletal involvement increased. The BSI provides a reproducible new parameter for quantitative assessment of bone involvement by AIPC. These results suggest that the BSI will be useful for stratifying patients entering treatment protocols for extent of tumor involvement of bone. Although further study is necessary, serial bone scan BSI appears capable of quantifying both the progression of bony involvement by tumor as well as the response to treatment.

Midazolam changes cerebral blood flow in discrete brain regions: an H2(15)O positron emission tomography study.

BACKGROUND: Changes in regional cerebral blood flow (rCBF) determined with H2(15)O positron emission tomographic imaging can identify neural circuits affected by centrally acting drugs. METHODS: Fourteen volunteers received one of two midazolam infusions adjusted according to electroencephalographic response. Low or high midazolam effects were identified using post-hoc spectral analysis of the electroencephalographic response obtained during positron emission tomographic imaging based on the absence or presence of 14-Hz spindle activity. The absolute change in global CBF was calculated, and relative changes in rCBF were determined using statistical parametric mapping with localization to standard stereotactic coordinates. RESULTS: The low-effect group received 7.5 +/- 1.7 mg midazolam (serum concentrations, 74 +/- 24 ng/ml), and the high-effect group received 9.7 +/- 1.3 mg midazolam (serum concentrations, 129 +/- 48 ng/ml). Midazolam decreased global CBF by 12% from 39.2 +/- 4.1 to 34.4 +/- 6.1 ml x 100 g(-1) x min(-1) (P < 0.02 at a partial pressure of carbon dioxide of 40 mmHg). The rCBF changes in the low-effect group were a subset of the high-effect group. Decreased rCBF (P < 0.001) occurred in the insula, the cingulate gyrus, multiple areas in the prefrontal cortex, the thalamus, and parietal and temporal association areas. Asymmetric changes occurred, particularly in the low-effect group, and were more significant in the left frontal cortex and thalamus and the right insula. Relative rCBF was increased in the occipital areas. CONCLUSION: Midazolam causes dose-related changes in rCBF in brain regions associated with the normal functioning of arousal, attention, and memory.