CT based quantitative measures of the stability of fractured metastatically involved vertebrae treated with spine stereotactic body radiotherapy.

Mechanical instability secondary to vertebral metastases can lead to pathologic vertebral compression fracture (VCF) mechanical pain, neurological compromise, and the need for surgical stabilization. Stereotactic body radiation therapy (SBRT) as a treatment for spinal metastases is effective for pain and local tumor control, it has been associated with an increased risk of VCF. This study quantified computed tomography (CT) based stability measures in metastatic vertebrae with VCF treated with spine SBRT. It was hypothesized that semi-automated quantification of VCF based on CT metrics would be related to clinical outcomes. 128 SBRT treated spinal metastases patients were identified from a prospective database. Of these, 18 vertebral segments were identified with a VCF post-SBRT. A semi-automated system for quantifying VCF was developed based on CT imaging before and after SBRT. The system identified and segmented SBRT treated vertebral bodies, calculated stability metrics at single time points and changes over time. In the vertebrae that developed a new (n = 7) or progressive (n = 11) VCF following SBRT, the median time to VCF/VCF progression was 1.74 months (range 0.53-7.79 months). Fractured thoracolumbar vertebrae that went on to be stabilized (cemented and/or instrumented), had greater fractured vertebral body volume progression over time (12%) compared to those not stabilized (0.4%, p < 0.05). Neither the spinal instability neoplastic score (SINS) or any single timepoint stability metrics in post-hoc analyses correlated with future stabilization. This pilot study presents a quantitative semi-automated method assessing fractured thoracolumbar vertebrae based on CT. Increased fractured vertebral body volume progression post-SBRT was shown to predict those patients who were subsequently stabilized, motivating study of methods that assess temporal radiological changes toward augmenting existing clinical management in the metastatic spine.

Design and construction of a quality control phantom for SPECT and PET imaging.

In this article, the authors present a method for quickly and easily constructing test phantoms for PET and SPECT quality assurance. As a demonstration, they constructed a complex prototype test phantom, showing the strengths of the construction method. Images taken using a PET/CT and a SPECT scanner are presented, along with a qualitative evaluation of PET/CT using the test phantom. The construction technique provides a quick, easy, and cost effective means of constructing a phantom for use in nuclear medicine imaging.

Prospective evaluation of pretreatment and intratreatment FDG PET-CT SUV stability in primary head and neck cancer.

PURPOSE: To evaluate standardized uptake value (SUV) stability on pretreatment and intratreatment 18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in patients undergoing definitive CRT for head and neck cancer (HNC). METHODS: Primary tumor and nodal volumes of interest (VOIs) from HNC patients were contoured on the pretreatment and intratreatment PET-CT by two independent observers. SUV stability was measured with intersection calculations (DICE, overlap fraction, center to center) between the VOIs at threshold levels of 50%, 60%, 70%, 80%, and 90% of the SUV maximum. RESULTS: The mean calculated DICE of the 50%, 60%, 70%, 80%, 90% SUV threshold was 0.53, 0.48, 0.41, 0.28, and 0.12, respectively. The mean calculated overlap fraction was 0.71, 0.65, 0.58, 0.43, and 0.2, respectively. Center-center difference demonstrates spatial variability of 7.8, 8.2, 8.6, 9.5, and 11.2 mm for these SUV subvolumes of interest. CONCLUSIONS: HNC subvolumes defined by SUV thresholding technique in FDG PET-CT imaging do not remain physically stable during (chemo)RT. HIGHLIGHTS: All pretreatment and intratreatment SUV thresholds (50%-90%) overlap indexes are low during the course of (chemo)radiation. Pretreatment and intratreatment center to center variation further corroborates that all FDG threshold volumes do not remain stable during treatment. No difference in SUV threshold stability was seen between p16 positive and negative tumors.

Frontal lobe hypoperfusion and depressive symptoms in Alzheimer disease.

BACKGROUND: Depressive symptoms of varying severity are prevalent in up to 63% of Alzheimer disease (AD) patients and often result in greater cognitive decline and increased caregiver burden. The current study aimed to determine the neural correlates of depressive symptoms in a sample of AD patients. METHODS: Using the Cornell Scale for Depression in Dementia, we assessed 56 patients who met criteria for probable AD. Data obtained from Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (SPECT) were analyzed with the use of a magnetic resonance imaging-derived region of interest (ROI) anatomic template before and after atrophy correction and statistical parametric mapping (SPM). The following 4 frontal ROIs were investigated bilaterally: middle frontal gyrus (Brodmann's area [BA] 46), orbitofrontal cortex (BA 11), superior prefrontal (BA 8/9) and anterior cingulate (BA 24/25/32/33). RESULTS: Depressive symptoms were present in 27 of the AD patients (48%). Patients with depressive symptoms showed less perfusion in the right superior and bilateral middle frontal gyri (p < 0.005), left superior frontal (p < 0.05) and anterior cingulate gyri (p < 0.005) before atrophy correction. SPM analyses revealed significantly lower perfusion in bilateral dorsolateral and superior prefrontal cortex of patients with depressive symptoms (right, p < 0.005; left, p < 0.05). SPECT ROI analyses with atrophy correction revealed trends similar to data without atrophy correction but did not reach statistical significance. CONCLUSION: In this study, depressive symptoms in AD patients were associated with relative hypoperfusion in the prefrontal cortex when they were compared with AD patients without depressive symptoms. These findings are consistent with previous reports in studies of primary depression suggesting that these regions are involved in affect and emotional regulation.

Experimental evaluation of an online gamma-camera imaging of permanent seed implantation (OGIPSI) prototype for partial breast irradiation.

Previously, our team used Monte Carlo simulation to demonstrate that a gamma camera could potentially be used as an online image guidance device to visualize seeds during permanent breast seed implant procedures. This could allow for intraoperative correction if seeds have been misplaced. The objective of this study is to describe an experimental evaluation of an online gamma-camera imaging of permanent seed implantation (OGIPSI) prototype. The OGIPSI device is intended to be able to detect a seed misplacement of 5 mm or more within an imaging time of 2 min or less. The device was constructed by fitting a custom built brass collimator (16 mm height, 0.65 mm hole pitch, 0.15 mm septal thickness) on a 64 pixel linear array CZT detector (eValuator-2000, eV Products, Saxonburg, PA). Two-dimensional projection images of seed distributions were acquired by the use of a digitally controlled translation stage. Spatial resolution and noise characteristics of the detector were measured. The ability and time needed for the OGIPSI device to image the seeds and to detect cold spots was tested using an anthropomorphic breast phantom. Mimicking a real treatment plan, a total of 52 103Pd seeds of 65.8 MBq each were placed on three different layers at appropriate depths within the phantom. The seeds were reliably detected within 30 s with a median error in localization of 1 mm. In conclusion, an OGIPSI device can potentially be used for image guidance of permanent brachytherapy applications in the breast and, possibly, other sites.

Online gamma-camera imaging of 103Pd seeds (OGIPS) for permanent breast seed implantation.

Permanent brachytherapy seed implantation is being investigated as a mode of accelerated partial breast irradiation for early stage breast cancer patients. Currently, the seeds are poorly visualized during the procedure making it difficult to perform a real-time correction of the implantation if required. The objective was to determine if a customized gamma-camera can accurately localize the seeds during implantation. Monte Carlo simulations of a CZT based gamma-camera were used to assess whether images of suitable quality could be derived by detecting the 21 keV photons emitted from 74 MBq (103)Pd brachytherapy seeds. A hexagonal parallel hole collimator with a hole length of 38 mm, hole diameter of 1.2 mm and 0.2 mm septa, was modeled. The design of the gamma-camera was evaluated on a realistic model of the breast and three layers of the seed distribution (55 seeds) based on a pre-implantation CT treatment plan. The Monte Carlo simulations showed that the gamma-camera was able to localize the seeds with a maximum error of 2.0 mm, using only two views and 20 s of imaging. A gamma-camera can potentially be used as an intra-procedural image guidance system for quality assurance for permanent breast seed implantation.

Contamination during a brachytherapy procedure.

This paper describes an unusual contamination incident that occurred during the treatment of a prostate cancer patient with seeds containing 125I. The incident became particularly interesting as the radiation safety procedures in place prior to the incident were, in fact, inappropriate for the type of incident that occurred, resulting in a series of response errors. Strands containing 108 125I seeds with a total activity of 1.61 GBq (43.6 mCi) were implanted into a patient's prostate and the patient was sent to the recovery room. A radiation survey detected radiation levels of up to 15 microR h(-1), 10 cm from the surface of the implantation needles. Multiple individuals entered the room and were potentially exposed to contamination. Contamination was detected in a sample of the patient's urine, indicating that one or more implanted seeds were leaking. Initial test results for staff showed that 12 of 15 had thyroid levels potentially above their corresponding minimum detectable activity levels, with calculated thyroid burdens ranging from 0.17 kBq to 0.94 kBq, but, subsequent measurements, using each staff member's thigh counts as background, suggested that no staff member had been contaminated. The patient showed high uptake of 125I in his neck 10 d following the incident, estimated to correspond to an initial thyroid burden of 58 kBq. The possibility of contamination was not immediately considered due to the suspicion of the more common problem of a misplaced source. The initial measurements suggesting thyroidal contamination in staff point to an error in our thyroid screening method.

Classification and evaluation strategies of auto-segmentation approaches for PET: Report of AAPM task group No. 211.

PURPOSE: The purpose of this educational report is to provide an overview of the present state-of-the-art PET auto-segmentation (PET-AS) algorithms and their respective validation, with an emphasis on providing the user with help in understanding the challenges and pitfalls associated with selecting and implementing a PET-AS algorithm for a particular application. APPROACH: A brief description of the different types of PET-AS algorithms is provided using a classification based on method complexity and type. The advantages and the limitations of the current PET-AS algorithms are highlighted based on current publications and existing comparison studies. A review of the available image datasets and contour evaluation metrics in terms of their applicability for establishing a standardized evaluation of PET-AS algorithms is provided. The performance requirements for the algorithms and their dependence on the application, the radiotracer used and the evaluation criteria are described and discussed. Finally, a procedure for algorithm acceptance and implementation, as well as the complementary role of manual and auto-segmentation are addressed. FINDINGS: A large number of PET-AS algorithms have been developed within the last 20 years. Many of the proposed algorithms are based on either fixed or adaptively selected thresholds. More recently, numerous papers have proposed the use of more advanced image analysis paradigms to perform semi-automated delineation of the PET images. However, the level of algorithm validation is variable and for most published algorithms is either insufficient or inconsistent which prevents recommending a single algorithm. This is compounded by the fact that realistic image configurations with low signal-to-noise ratios (SNR) and heterogeneous tracer distributions have rarely been used. Large variations in the evaluation methods used in the literature point to the need for a standardized evaluation protocol. CONCLUSIONS: Available comparison studies suggest that PET-AS algorithms relying on advanced image analysis paradigms provide generally more accurate segmentation than approaches based on PET activity thresholds, particularly for realistic configurations. However, this may not be the case for simple shape lesions in situations with a narrower range of parameters, where simpler methods may also perform well. Recent algorithms which employ some type of consensus or automatic selection between several PET-AS methods have potential to overcome the limitations of the individual methods when appropriately trained. In either case, accuracy evaluation is required for each different PET scanner and scanning and image reconstruction protocol. For the simpler, less robust approaches, adaptation to scanning conditions, tumor type, and tumor location by optimization of parameters is necessary. The results from the method evaluation stage can be used to estimate the contouring uncertainty. All PET-AS contours should be critically verified by a physician. A standard test, i.e., a benchmark dedicated to evaluating both existing and future PET-AS algorithms needs to be designed, to aid clinicians in evaluating and selecting PET-AS algorithms and to establish performance limits for their acceptance for clinical use. The initial steps toward designing and building such a standard are undertaken by the task group members.

The influence of sex on limbic volume and perfusion in AD.

The goal of the current study was to determine whether Alzheimer's disease (AD) pathology affects the limbic system of men and women differently as measured by in vivo neuroimaging. Magnetic resonance imaging (MRI) and coregistered single photon emission computed tomography (SPECT) were used to examine the limbic system in 20 men and 20 women with probable AD compared to 40 age- and education-matched normal controls (20 men, 20 women). Limbic volumes and relative perfusion values were obtained from the MR images and coregistered SPECT scans, respectively. No significant differences were found between sexes in limbic volumes or relative perfusion values in the normal controls. Many limbic regions were significantly affected in both men and women with AD compared to normal controls. However, only the men with AD displayed atrophy in the orbitofrontal cortex, middle and posterior cingulate cortices, hypothalamus, and mamillary bodies, and relative hypoperfusion in the anterior and middle cingulate cortices. Women with AD exclusively showed anterior thalamic atrophy. Separating men and women did not substantially improve diagnostic classification.

Medial temporal hypoperfusion and aggression in Alzheimer disease.

BACKGROUND: It is not understood why some patients with Alzheimer disease (AD) display aggression and others do not. OBJECTIVE: To examine the relation between regional brain perfusion and aggression in AD. DESIGN: Single-photon emission computed tomographic scans were coregistered to a standardized template in Talairach space, generating mean ratios of uptake referenced to the cerebellum. PARTICIPANTS: Forty-nine outpatients (25 men and 24 women; mean +/- SD age, 74 +/- 11 years) with probable AD (Mini-Mental State Examination score, 17.7 +/- 5.0; 30 aggressive and 19 nonaggressive), comparable in age, sex, and severity of cognitive impairment. MAIN OUTCOME MEASURES: Regional perfusion ratios were determined for 5 bilateral regions of interest: orbitofrontal, middle medial temporal, inferior medial temporal, hypothalamus/thalamus, and anterior cingulate. RESULTS: Compared with nonaggressive patients, aggressive ones displayed hypoperfusion in the right and left middle medial temporal regions of interest (P = .02 for both), but not the others (all (t tests, unpaired, 2-tailed). On regression analyses, right middle temporal hypoperfusion (P = .001), younger age (P = .002), greater activity disturbances (P = .004), and higher Mini-Mental State Examination scores (P = .04) independently predicted aggression, accounting for 44% of the total variance (F = 8.7; P<.001). Statistical parametric mapping analyses supported right middle medial temporal hypoperfusion in the aggressive group (P = .008). CONCLUSION: In this sample of patients with AD, the right middle medial temporal region emerged as an important neural correlate of aggression.

Can PET provide the 3D extent of tumor motion for individualized internal target volumes? A phantom study of the limitations of CT and the promise of PET.

PURPOSE: To characterize the limitations of fast, spiral computed tomography (CT) when imaging a moving object and to investigate whether positron emission tomography (PET) can predict the internal target volume (ITV) and ultimately improve the planning target volume (PTV) for moving tumors. METHODS AND MATERIALS: To mimic tumors, three fillable spheres were imaged while both stationary and during periodic motion using spiral CT and PET. CT- and PET-imaged volumes were defined quantitatively using voxel values. Ideal PTVs for each scenario were calculated. CT-based PTVs were generated using margins of 7.5, 10, and 15 mm to account for both organ motion and setup uncertainties. PET-based PTVs were derived with the assumption that motion was captured in the PET images and only a margin (7.5 mm) for setup errors was necessary. Comparisons between CT-based and PET-based PTVs with ideal PTVs were performed. RESULTS: CT imaging of moving spheres resulted in significant distortions in the three-dimensional (3D) image-based representations, and did not, in general, result in images well representative of either moving or stationary spheres. PET images were similar to the ideal capsular shape encompassing the sphere and its motion. In all cases, CT-imaged volumes were larger than that for the stationary sphere (range of excess volume from 0.4 to 29 cm(3) for stationary volumes of 2.14 to 172 cm(3)), but smaller than that for the true motion volume. PET-imaged volumes were larger than the true motion volume (difference from ideal ranged from 3 to 94 cm(3) for motion volumes of 1.2 to 243 cm(3)) and much larger than the stationary volume. Using CT data, geographic miss of some part of the ideal PTV occurred for 0 of 24 cases, 11 of 24 cases, and 18 of 24 cases using a 15-mm, 10-mm, and 7.5-mm margin, respectively. Geographic miss did not occur in any case for the PET-based PTV. The amount of "normal tissue" included in CT-based PTVs was dramatically greater than that included in PET-based PTVs. CONCLUSION: Fast CT imaging of a moving tumor can result in poor representation of the time-averaged position and shape of the tumor. PET imaging can provide a more accurate representation of the 3D volume encompassing motion of model tumors and has potential to provide patient-specific motion volumes for an individualized ITV.

The impact of (18)FDG-PET on target and critical organs in CT-based treatment planning of patients with poorly defined non-small-cell lung carcinoma: a prospective study.

PURPOSE: To prospectively study the impact of coregistering (18)F-fluoro-deoxy-2-glucose hybrid positron emission tomographic (FDG-PET) images with CT images on the planning target volume (PTV), target coverage, and critical organ dose in radiation therapy planning of non-small-cell lung carcinoma. METHODS AND MATERIALS: Thirty patients with poorly defined tumors on CT, referred for radical radiation therapy, underwent both FDG-PET and CT simulation procedures on the same day, in radiation treatment position. Image sets were coregistered using external fiducial markers. Three radiation oncologists independently defined the gross tumor volumes, using first CT data alone and then coregistered CT and FDG-PET data. Standard margins were applied to each gross tumor volume to generate a PTV, and standardized treatment plans were designed and calculated for each PTV. Dose-volume histograms were used to evaluate the relative effect of FDG information on target coverage and on normal tissue dose. RESULTS: In 7 of 30 (23%) cases, FDG-PET information changed management strategy from radical to palliative. In 5 of the remaining 23 (22%) cases, new FDG-avid nodes were found within 5 cm of the primary tumor and were included in the PTV. The PTV defined using coregistered CT and FDG-PET would have been poorly covered by the CT-based treatment plan in 17--29% of cases, depending on the physician, implying a geographic miss had only CT information been available. The effect of FDG-PET on target definition varied with the physician, leading to a reduction in PTV in 24-70% of cases and an increase in 30-76% of cases. The relative change in PTV ranged from 0.40 to 1.86. On average, FDG-PET information led to a reduction in spinal cord dose but not in total lung dose, although large differences in dose to the lung were seen for a few individuals. CONCLUSION: The coregistration of planning CT and FDG-PET images made significant alterations to patient management and to the PTV. Ultimately, changes to the PTV resulted in changes to the radiation treatment plans for the majority of cases. Where possible, we would recommend that FDG-PET data be integrated into treatment planning of non-small-cell lung carcinoma, particularly for three-dimensional conformal techniques.

Utility of simultaneous brain, CSF and hyperintensity quantification in dementia.

Improved methods of quantifying MRI are needed to study brain-behavior relationships in dementia. Rating scales are variable; lesion-tracing approaches can be subjective and ignore atrophy; segmentation of MRI hyperintensities is complicated by partial volume effects; and hyperintense lesions in different anatomical areas may have different effects. The goal of this study was to extend existing segmentation approaches to include hyperintensities and to demonstrate the utility of simultaneously assessing atrophy and lesion compartments in dementia. A semi-automated method was applied to quantify brain and cerebrospinal fluid (CSF) compartments and to subclassify hyperintensities into periventricular, deep white matter, thalamic and basal ganglia compartments. Twenty MR scans from participants in an ongoing dementia study were used to generate intra- and inter-rater reliability estimates. High intra- and inter-class correlation coefficients (0.83-0.99) were obtained for all measures and the semi-automated measurements were highly correlated with traced volumes. Brain, CSF and specific lesion volumes were significantly correlated with neuropsychological functions. In models using only total hyperintensity volumes, the effects of lesion compartments (such as thalamic) were masked. Simultaneous quantification of atrophy and anatomically distinct hyperintensities is important for understanding cognitive impairments in dementia.