Thomas K. Lewellen

PET-CT image registration in the chest using free-form deformations

We have implemented and validated an algorithm for three-dimensional positron emission tomography transmission-to-computed tomography registration in the chest, using mutual information as a similarity criterion. Inherent differences in the two imaging protocols produce significant nonrigid motion between the two acquisitions. A rigid body deformation combined with localized cubic B-splines is used to capture this motion. The deformation is defined on a regular grid and is parameterized by potentially several thousand coefficients. Together with a spline-based continuous representation of images and Parzen histogram estimates, our deformation model allows closed-form expressions for the criterion and its gradient. A limited-memory quasi-Newton optimization algorithm is used in a hierarchical multiresolution framework to automatically align the images. To characterize the performance of the method, 27 scans from patients involved in routine lung cancer staging were used in a validation study. The registrations were assessed visually by two expert observers in specific anatomic locations using a split window validation technique. The visually reported errors are in the 0- to 6-mm range and the average computation time is 100 min on a moderate-performance workstation.

Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: A pretherapy study of 37 patients

PURPOSE To assess pretreatment hypoxia in a variety of tumors using positron emission tomography (PET) after injection of the hypoxia-binding radiopharmaceutical [18F]fluoromisonidazole ([18F]FMISO). METHODS AND MATERIALS Tumor fractional hypoxic volume (FHV) was determined in 21 nonsmall cell lung cancer patients, 7 head and neck cancer patients, 4 prostate cancer patients, and 5 patients with other malignancies by quantitative PET imaging after injection of [18F]FMISO (0.1 mCi/kg). The FHV was defined as the proportion of pixels in the imaged tumor volume with a tissue:blood [18F] activity ratio > or = 1.4 at 120-160 min postinjection. A FHV > 0 was taken as evidence for tumor hypoxia. RESULTS Hypoxia was observed in 36 of 37 tumors studied with FMISO PET imaging; FHVs ranged from 0 to 94.7%. In nonsmall cell lung cancers (n = 21), the median FHV was 47.6% and the range, 1.3 to 94.7%. There was no correlation between tumor size and FHV. In the seven head and neck carcinomas, the median FHV was 8.8%, with a range from 0.2 to 18.9%. In the group of four prostate cancers, the median and range were 18.2% and 0 to 93.9%, while in a group of five tumors of different types the median FHV was 55.2% (range: 21.4 to 85.8%). CONCLUSIONS Hypoxia was present in 97% of the tumors studied and the extent of hypoxia varied markedly between tumors in the same site or of the same histology. Hypoxia also was distributed heterogeneously between regions within a single tumor. These results are consistent with O2 electrode measures with other types of human tumors. The intra- and intertumor variability indicate the importance of making oxygenation measures in individual tumors and the necessity to sample as much of the tumor volume as possible.

l Brief Communication QUANTIFYING REGIONAL HYPOXIA IN HUMAN TUMQRS WITH POSITRON EMISSION TOMOGRAPHY OF ('*F)FLUUROMISONIDAZOLE: A PRETHERAPY STUDY OF 37 PATIENTS

PURPOSE To assess pretreatment hypoxia in a variety of tumors using positron emission tomography (PET) after injection of the hypoxia-binding radiopharmaceutical [18F]fluoromisonidazole ([18F]FMISO). METHODS AND MATERIALS Tumor fractional hypoxic volume (FHV) was determined in 21 nonsmall cell lung cancer patients, 7 head and neck cancer patients, 4 prostate cancer patients, and 5 patients with other malignancies by quantitative PET imaging after injection of [18F]FMISO (0.1 mCi/kg). The FHV was defined as the proportion of pixels in the imaged tumor volume with a tissue:blood [18F] activity ratio > or = 1.4 at 120-160 min postinjection. A FHV > 0 was taken as evidence for tumor hypoxia. RESULTS Hypoxia was observed in 36 of 37 tumors studied with FMISO PET imaging; FHVs ranged from 0 to 94.7%. In nonsmall cell lung cancers (n = 21), the median FHV was 47.6% and the range, 1.3 to 94.7%. There was no correlation between tumor size and FHV. In the seven head and neck carcinomas, the median FHV was 8.8%, with a range from 0.2 to 18.9%. In the group of four prostate cancers, the median and range were 18.2% and 0 to 93.9%, while in a group of five tumors of different types the median FHV was 55.2% (range: 21.4 to 85.8%). CONCLUSIONS Hypoxia was present in 97% of the tumors studied and the extent of hypoxia varied markedly between tumors in the same site or of the same histology. Hypoxia also was distributed heterogeneously between regions within a single tumor. These results are consistent with O2 electrode measures with other types of human tumors. The intra- and intertumor variability indicate the importance of making oxygenation measures in individual tumors and the necessity to sample as much of the tumor volume as possible.

Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography

PURPOSE Recent clinical investigations have shown a strong correlation between pretreatment tumor hypoxia and poor response to radiotherapy. These observations raise questions about standard assumptions of tumor reoxygenation during radiotherapy, which has been poorly studied in human cancers. Positron emission tomography (PET) imaging of [F-18]fluoromisonidazole (FMISO) uptake allows noninvasive assessment of tumor hypoxia, and is amenable for repeated studies during fractionated radiotherapy to systematically evaluate changes in tumor oxygenation. METHODS AND MATERIALS Seven patients with locally advanced nonsmall cell lung cancers underwent sequential [F-18]FMISO PET imaging while receiving primary radiotherapy. Computed tomograms were used to calculate tumor volumes, define tumor extent for PET image analysis, and assist in PET image registration between serial studies. Fractional hypoxic volume (FHV) was calculated for each study as the percentage of pixels within the analyzed imaged tumor volume with a tumor:blood [F-18]FMISO ratio > or = 1.4 by 120 min after injection. Serial FHVs were compared for each patient. RESULTS Pretreatment FHVs ranged from 20-84% (median 58%). Subsequent FHVs varied from 8-79% (median 29%) at midtreatment, and ranged from 3-65% (median 22%) by the end of radiotherapy. One patient had essentially no detectable residual tumor hypoxia by the end of radiation, while two others showed no apparent decrease in serial FHVs. There was no correlation between tumor size and pretreatment FHV. CONCLUSIONS Although there is a general tendency toward improved oxygenation in human tumors during fractionated radiotherapy, these changes are unpredictable and may be insufficient in extent and timing to overcome the negative effects of existing pretreatment hypoxia. Selection of patients for clinical trials addressing radioresistant hypoxic cancers can be appropriately achieved through single pretreatment evaluations of tumor hypoxia.

Recent developments in PET detector technology

Positron emission tomography (PET) is a tool for metabolic imaging that has been utilized since the earliest days of nuclear medicine. A key component of such imaging systems is the detector modules--an area of research and development with a long, rich history. Development of detectors for PET has often seen the migration of technologies, originally developed for high energy physics experiments, into prototype PET detectors. Of the many areas explored, some detector designs go on to be incorporated into prototype scanner systems and a few of these may go on to be seen in commercial scanners. There has been a steady, often very diverse development of prototype detectors, and the pace has accelerated with the increased use of PET in clinical studies (currently driven by PET/CT scanners) and the rapid proliferation of pre-clinical PET scanners for academic and commercial research applications. Most of these efforts are focused on scintillator-based detectors, although various alternatives continue to be considered. For example, wire chambers have been investigated many times over the years and more recently various solid-state devices have appeared in PET detector designs for very high spatial resolution applications. But even with scintillators, there have been a wide variety of designs and solutions investigated as developers search for solutions that offer very high spatial resolution, fast timing, high sensitivity and are yet cost effective. In this review, we will explore some of the recent developments in the quest for better PET detector technology.

Depth of interaction decoding of a continuous crystal detector module

We present a clustering method to extract the depth of interaction (DOI) information from an 8 mm thick crystal version of our continuous miniature crystal element (cMiCE) small animal PET detector. This clustering method, based on the maximum-likelihood (ML) method, can effectively build look-up tables (LUT) for different DOI regions. Combined with our statistics-based positioning (SBP) method, which uses a LUT searching algorithm based on the ML method and two-dimensional mean-variance LUTs of light responses from each photomultiplier channel with respect to different gamma ray interaction positions, the position of interaction and DOI can be estimated simultaneously. Data simulated using DETECT2000 were used to help validate our approach. An experiment using our cMiCE detector was designed to evaluate the performance. Two and four DOI region clustering were applied to the simulated data. Two DOI regions were used for the experimental data. The misclassification rate for simulated data is about 3.5% for two DOI regions and 10.2% for four DOI regions. For the experimental data, the rate is estimated to be approximately 25%. By using multi-DOI LUTs, we also observed improvement of the detector spatial resolution, especially for the corner region of the crystal. These results show that our ML clustering method is a consistent and reliable way to characterize DOI in a continuous crystal detector without requiring any modifications to the crystal or detector front end electronics. The ability to characterize the depth-dependent light response function from measured data is a major step forward in developing practical detectors with DOI positioning capability.

Design of a depth of interaction (DOI) PET detector module

A method to determine depth of interaction (DOI) from a PET detector module is described and evaluated. The basic element of the DOI detector module is a two crystal detector unit. The hypothesis is that by controlling how light is shared between two crystals (A and B) DOI information can be extracted from the ratio of light collected using simple Anger logic [(A-B)/(A+B)]. The interface between crystals is designed so that a significant amount of light is shared when a photon interacts near the front face of a crystal and very little light is shared when an interaction occurs near the back of a crystal. The effects of surface treatment (e.g., polished, roughened) and optical coupling compounds are investigated. BGO, GSO and LSO detector units have been evaluated. A DOI uncertainty of /spl sim/6 mm was attained for the front section (/spl sim/4 mm) of a 2/spl times/2/spl times/20 mm LSO detector unit. A method to decode a 64 crystal detector module (32 detector units) using a 16 channel multi-anode photomultiplier tube is described.

Modeling and incorporation of system response functions in 3-D whole body PET

Appropriate application of spatially variant system models can correct for degraded resolution response and mispositioning errors. This paper explores the detector blurring component of the system model for a whole body positron emission tomography (PET) system and extends this factor into a more general system response function to account for other system effects including the influence of Fourier rebinning (FORE). We model the system response function as a three-dimensional (3-D) function that blurs in the radial and axial dimension and is spatially variant in radial location. This function is derived from Monte Carlo simulations and incorporates inter-crystal scatter, crystal penetration, and the blurring due to the FORE algorithm. The improved system model is applied in a modified ordered subsets expectation maximization (OSEM) algorithm to reconstruct images from rebinned, fully 3-D PET data. The proposed method effectively removes the spatial variance in the resolution response, as shown in simulations of point sources. Furthermore, simulation and measured studies show the proposed method improves quantitative accuracy with a reduction in tumor bias compared to conventional OSEM on the order of 10%-30% depending on tumor size and smoothing parameter

The use of importance sampling techniques to improve the efficiency of photon tracking in emission tomography simulations.

Monte Carlo simulations are widely used to study the transmission and scattering of gamma rays. Use of this method for simulations of emission tomographs suffers from geometric inefficiency resulting from the low solid angle of acceptance of most tomograph designs. We have applied several importance sampling techniques--stratification, forced detection, and weight control through Russian roulette and splitting--to increase the computational efficiency of the Monte Carlo method 10- to 300-fold. A description of these techniques, their validation, and sample performance results are given. Application of importance sampling methods makes it practical to study photon scattering in heterogeneous attenuators on workstations and minicomputers.

Clinical Imaging Characteristics of the Positron Emission Mammography Camera: PEM Flex Solo II

We evaluated a commercial positron emission mammography (PEM) camera, the PEM Flex Solo II. This system comprises two 6 × 16.4 cm detectors that scan together covering up to a 24 × 16.4 cm field of view (FOV). There are no specific standards for testing this detector configuration. We performed several tests important to breast imaging, and we propose tests that should be included in standardized testing of PEM systems. Methods: We measured spatial resolution, uniformity, counting- rate linearity, recovery coefficients, and quantification accuracy using the systems software. Image linearity and coefficient of variation at the edge of the FOV were also characterized. Anecdotal examples of clinical patient data are presented. Results: The spatial resolution was 2.4 mm in full width at half maximum for image planes parallel to the detector faces. The background variability was approximately 5%, and quantification accuracy and recovery coefficients varied within the FOV. Positioning linearity began at approximately 13 mm from the edge of the detector housing. The coefficient of variation was significantly higher close to the edge of the FOV because of limited sensitivity in these image planes. Conclusion: A reconstructed spatial resolution of 2.4 mm represented a significant improvement over conventional whole-body PET scanners and should reduce the lower threshold on lesion size and tracer uptake for detection in the breast. Limited-angle tomography and a lack of data corrections result in spatially variable quantitative results. PEM acquisition geometry limits sampling statistics at the chest-wall edge of the camera, resulting in high variance in that portion of the image. Example patient images demonstrate that lesions can be detected at the chest-wall edge despite variance artifacts, and fine structure is visualized routinely throughout the FOV in the focal plane. The PEM Flex camera should enable the functional imaging of breast cancer earlier in the disease process than whole-body PET.