Bill C. Penney

Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer.

OBJECTIVE To assess the prognostic value of metabolic tumor burden as measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT), independent of current Union Internacional Contra la Cancrum/American Joint Committee on Cancer tumor, node, and metastasis (TNM) stage; in comparison with that of standardized uptake value (SUV) in surgical patients with non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS This study retrospectively reviewed 104 consecutive surgical patients (47 males, 57 females, median age at PET/CT scan of 67.92 years) with diagnosed stage I to IV NSCLC who had baseline (18)F-FDG PET/CT scans. The (18)F-FDG PET/CT scans were performed in accordance with National Cancer Institute guidelines. The MTV of tumors in the whole body (MTV(WB)), TLG of tumors in the whole body (TLG(WB)), the maximum standardized uptake value of tumors in the whole body (SUV(maxWB)) as well as the mean standardized uptake value of tumor in the whole body (SUV(meanWB)) were measured. The median follow-up among 67 survivors was 42.07 months from the PET/CT (range 2.82-80.95 months). Statistical methods included Kaplan-Meier curves, Cox regression, and C-statistics. The interobserver variability of SUV(maxWB), SUV(meanWB), MTV(WB), and TLG(WB) between two observers was analyzed using concordance correlation coefficients (CCCs). RESULTS The interobserver variability of SUV(maxWB), SUV(meanWB), MTV(WB) and TLG(WB) was very low with CCCs greater than 0.882. There was a statistically significant association of stage with overall survival (OS). The hazard ratio (HR) of stage III and stage IV as compared with stage I was 3.60 (P = .001) and 4.00 (P = .013), respectively. The MTV(WB) was significantly associated with OS with a HR for 1-unit increase of ln(MTV(WB)) of 1.40/1.32 (P = .004/.039), before/after adjusting for stage and other prognostic factors including chemoradiation therapy, and surgical procedure, respectively. TLG(WB) had a statistically significant association with OS before and after adjusting for stage and the other prognostic factors. The HR for 1-unit increase in ln(TLG(WB)) was 1.26 (P = .011) and 1.25 (P = .031), before and after the adjustment, respectively. Subjects with conditions that led to pneumonectomy (HR = 2.82, P = .035) or segmental resection (HR = 3.44, P = .044) had significantly worse survival than those needing lobectomy. There was no statistically significant association between OS and age, gender, tumor histology, ln(SUV(maxWB)), and ln(SUV(meanWB)) (all P > .05). There were 37 deaths during follow-up. CONCLUSION Baseline whole-body metabolic tumor burden as measured with MTV(WB) and TLG(WB) on FDG PET is a prognostic measure independent of clinical stage and other prognostic factors including chemoradiation therapy and surgical procedure with low interobserver variability and may be used to further risk stratify surgical patients with NSCLC. This study also suggests that MTV and TLG are better prognostic measures than SUV(max) and SUV(mean). These results will need to be validated in larger cohorts in a prospective study.

Noniterative compensation for the distance-dependent detector response and photon attenuation in SPECT imaging

A filtering approach is described, which accurately compensates for the 2D distance-dependent detector response, as well as for photon attenuation in a uniform attenuating medium. The filtering method is based on the frequency distance principle (FDP) which states that points in the object at a specific source-to-detector distance provide the most significant contribution to specified frequency regions in the discrete Fourier transform (DFT) of the sinogram. By modeling the detector point spread function as a 2D Gaussian function whose width is dependent on the source-to-detector distance, a spatially variant inverse filter can be computed and applied to the 3D DFT of the set of all sinogram slices. To minimize noise amplification the inverse filter is rolled off at high frequencies by using a previously published Wiener filter strategy. Attenuation compensation is performed with Bellinis method. It was observed that the tomographic point response, after distance-dependent filtering with the FDP, was approximately isotropic and varied substantially less with position than that obtained with other correction methods. Furthermore, it was shown that processing with this filtering technique provides reconstructions with minimal degradation in image fidelity.

Prognostic Value of the Quantitative Metabolic Volumetric Measurement on 18F-FDG PET/CT in Stage IV Nonsurgical Small-cell Lung Cancer

RATIONALE AND OBJECTIVES Stage IV non-small-cell lung cancer (NSCLC) consists of a heterogeneous group of patients with different prognoses. We assessed the prognostic value of baseline whole body tumor burden as measured by metabolic tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake values (SUV(max) and SUV(mean)) of all tumors in nonsurgical patients with Stage IV NSCLC. MATERIALS AND METHODS Ninety-two consecutive patients with newly diagnosed Stage IV NSCLC who had a pretreatment F-18 fludeoxyglucose positron emission tomography/computed tomography scan were retrospectively reviewed. The MTV, TLG, SUV(mean), and SUV(max) of whole-body (WB) tumors were measured with the MIMvista workstation with manual adjustment. RESULTS There was a statistically significant association between overall survival (OS) and ln(MTV)/ln(TLG) at the level of WB tumor burden (MTV(WB)) and of primary tumor (MTV(T)). The hazard ratio (HR) for a 1-unit increase of ln(MTV(WB)) and ln(MTV(T)) before and after adjusting for age and gender was 1.48/1.48 (both P < .001) and 1.25/1.25 (P = .006, .007), respectively. The HR for a 1-unit increase of ln(TLG(WB)) and ln(TLG(T)) before and after adjusting for age and gender was 1.37/1.37 (both P = .001) and 1.19/1.19 (P = .001, .017), respectively. There was no statistically significant association between OS and ln(SUV(max)) and ln(SUV(mean)) at WB tumor burden, primary tumor, nodal metastasis, or distant metastasis (P > .05). There was low interobserver variability between two radiologists with concordance correlation coefficients of 0.90 for ln(MTV(WB)) and greater than 0.90 for SUV(maxWB), SUV(meanWB), and ln(TLG(WB)). CONCLUSION Baseline WB metabolic tumor burden, as measured with MTV and TLG, is a prognostic measurement in patients within Stage IV NSCLC with low interobserver variability. This study also suggests pretreatment MTV and TLG measurements may be used to further stratify patients with Stage IV NSCLC and are better prognostic measures than SUV(max) and SUV(mean) measurements.

Restoration of combined conjugate images in SPECT: comparison of a new Wiener filter and the image-dependent Metz filter

Two image-dependent restoration filters were applied to projection image sets obtained with single-photon-emission computed tomography (SPECT). Wiener and Metz restorations of combined conjugate views are compared to each other, Wiener restoration of individual projection images, and one-dimensional Butterworth smoothing. The combined view restoration filters adapt to the average thickness of the object by estimating a modulation transfer function (MTF) for that thickness. Simulated Tc-99m liver-spleen studies with randomly placed cold spot tumors, a projector which accounts for the spatially variant blurring in SPECT, and a Poisson noise generator are used to compute simulated projection image sets. These sets are filtered and reconstructed using the method of intrinsic attenuation correction of Tanaka et al. (1984). Cold spot contrast, automated receiver operator characteristic (ROC) analysis of cold spot detectability, and the normalized mean squared error (NMSE) are used to compare the four processing methods. Little difference is noted between the three restoration methods. However, the restoration filters all yield noticeably better ROC and NMSE results than the one-dimensional smoothing. Inspection of the three-dimensional MTF derived from reconstructions of point sources indicates that the restoration filters substantially reduce the low-frequency degradation which is primarily due to scatter. >

A projector, backprojector pair which accounts for the two-dimensional depth and distance dependent blurring in SPECT

The speed and accuracy of iterative reconstruction routines for single-photon-emission computed tomography (SPECT) are highly dependent on the projection and backprojection algorithms used. A projector-backprojector pair which accounts for the two-dimensional, spatially dependent blurring encountered in SPECT and which reduces the computational load has been developed. These algorithms assume that the attenuator is a uniform elliptical cylinder that is invariant in the axial direction. They further assume that the blur can be modeled using the sum of several separable functions, e.g. separate Gaussian functions for the geometric and scatter components. When implemented on an array processor of moderate computational power, a projection or backprojection of a SPECT study, with 64 64-pixel*64-pixel projection images and a 64*64*64 reconstruction space, can be completed in less than 2.4 h, or 2.3 min per transverse slice. >

Activity quantitation in SPECT : a study of prereconstruction Metz filtering and use of the scatter degradation factor

A study of activity quantitation with prereconstruction Metz filtering and use of the scatter degradation factor (SDF) to numerically correct for scatter was conducted. The ratio of the count rate per unit activity for source locations within a 30 x 23-cm water-filled tub phantom to the count rate per unit activity for Tc-99m point sources of known activity imaged in air was used to judge the accuracy of activity determination. The investigation was conducted for certain locations within the tub when it was uniformly filled with Tc-99m activity, and for the same locations at the center of 5, 4, 3, and 2-cm diam, hot spheres imaged in a cold background. The source locations were the center, and one-fourth, one-half, and three-fourths the major axis. Various methods of combining the conjugate views for use with prereconstruction attenuation correction (arithmetic and geometric mean), and extent to which the Metz filter followed the inverse filter before rolling off to suppress noise were investigated. Without Metz filtering, attenuation correction was performed using a transmission curve that included buildup. With Metz filtering, the good-geometry attenuation coefficient was used and the combined views were scaled by the SDF calculated for the average body thickness. Depending on the size of the sphere and the extent to which the inverse filter was followed, Metz filtering combined with use of the SDF improved the accuracy of activity quantitation.

The development and testing of a digital PET phantom for the evaluation of tumor volume segmentation techniques.

Methods for accurate tumor volume segmentation of positron emission tomography (PET) images have been under investigation in recent years partly as a result of the increased use of PET in radiation treatment planning (RTP). None of the developed automated or semiautomated segmentation methods, however, has been shown reliable enough to be regarded as the standard. One reason for this is that there is no source of well characterized and reliable test data for evaluating such techniques. The authors have constructed a digital tumor phantom to address this need. The phantom was created using the Zubal phantom as input to the SimSET software used for PET simulations. Synthetic tumors were placed in the lung of the Zubal phantom to provide the targets for segmentation. The authors concentrated on the lung, since much of the interest to include PET in RTP is for nonsmall cell lung cancer. Several tests were performed on the phantom to ensure its close resemblance to clinical PET scans. The authors measured statistical quantities to compare image intensity distributions from regions-of-interest (ROIs) placed in the liver, the lungs, and tumors in phantom and clinical reconstructions. Using ROIs they also made measurements of autocorrelation functions to ensure the image texture is similar in clinical and phantom data. The authors also compared the intensity profile and appearance of real and simulated uniform activity spheres within uniform background. These measurements, along with visual comparisons of the phantom with clinical scans, indicate that the simulated phantom mimics reality quite well. Finally, they investigate and quantify the relationship between the threshold required to segment a tumor and the inhomogeneity of the tumors image intensity distribution. The tests and various measurements performed in this study demonstrate how the phantom can offer a reliable way of testing and investigating tumor volume segmentation in PET.

Variation of the count-dependent Metz filter with imaging system modulation transfer function

A systematic investigation was conducted of how a number of parameters which alter the system modulation transfer function (MTF) influence the count-dependent Metz filter. Since restoration filters are most effective at those frequencies where the object power spectrum dominates that of the noise, it was observed that parameters which significantly degrade the MTF at low spatial frequencies strongly influence the formation of the Metz filter. Thus the radionuclide imaged and the depth of the source in a scattering medium had the most influence. This is because they alter the relative amount of scattered radiation being imaged. For low-energy photon emitters, the collimator employed and the distance from the collimator were found to have less of an influence but still to be significant. These cause alterations in the MTF which are more gradual, and hence are most pronounced at mid to high spatial frequencies. As long as adequate spatial sampling is employed, the Metz filter was determined to be independent of the exact size of the sampling bin width, to a first approximation. For planar and single photon emission computed tomographic (SPECT) imaging, it is shown that two-dimensional filtering with the Metz filter optimized for the imaging conditions is able to deconvolve scatter and other causes of spatial resolution loss while diminishing noise, all in a balanced manner.

Reaction of truncation artifacts in fan beam transmission imaging using a spatially varying gamma prior

Using fan beam transmission imaging to obtain an attenuation estimate of an object for attenuation correction is limited because the object may not be completely in the field of view of the camera at all angles. This truncation of object data creates artifacts in the attenuation map during reconstruction which may result in problems in the attenuation correction of the emission image. To improve the quality of the attenuation map, the authors have used information from the scatter window reconstruction of projections from a parallel hole collimator on one of the heads of the SPECT system. This scatter window reconstruction is used to create a segmentation-based attenuation map of the object. The authors use this map as a pixel-by-pixel gamma prior to aid in the iterative reconstruction of the final attenuation map. In the fully sampled central region, use of the segmentation map information is unnecessary; but in the poorly sampled, outer region, the use of the segmentation map is essential to obtain an accurate reconstruction. The authors use a spatially varying weight function for the gamma prior to reflect their confidence in the transmission in the central region while emphasizing the prior in the outer region. The result is a high-quality density map over both the fully sampled and poorly sampled regions. Furthermore, since the line integrals for the transmission data are preserved in the iterative reconstruction, the algorithm does not require precise determinations of the attenuation coefficients in the segmentation maps to create an accurate attenuation map.

Relative importance of the error sources in Wiener restoration of scintigrams

Through simulation studies, the relative importance of three error sources in Wiener filtering as applied to scintigrams is quantified. The importance of these error sources has been quantified using the percentage changed in squared error (compared to that of an image restored using an ideal Wiener filter) which is caused by estimating one of three factors in the Wiener filter. Estimating the noise power spectrum using the total image count produced to appreciable change in the squared error (less than 1%). Estimating the power spectrum of the true image from that of the degraded image produced small to moderate increases in the squared error (4-139%). In scintigraphic imaging, the modular transfer function (MTF) is dependent on source depth; hence, this study underscores the importance of using methods which reduce the depth dependence of the effective MTF prior to applying restoration filters. A novel method of estimating the power spectrum of the true image from that of the degraded images is also described and evaluated. Wiener restoration filters based on this spectral estimation method are found to be competitive with the image-dependent Metz restoration filter.