Summary: Accuracy in in vivo quantitation of brain func tion with positron emission tomography (PET) has often been limited by partial volume effects. This limitation be comes prominent in studies of aging and degenerative brain diseases where partial volume effects vary with dif ferent degrees of atrophy. The present study describes how the actual gray matter (GM) tracer concentration can be estimated using an algorithm that relates the regional fraction of GM to partial volume effects. The regional fraction of GM was determined by magnetic resonance imaging (MRI). The procedure is designated as GM PET. In computer simulations and phantom studies, the GM PET algorithm permitted a 100% recovery of the actual tracer concentration in neocortical GM and hippocam pus, irrespective of the GM volume. GM PET was apPositron emission tomography (PET) permits in vestigation of physiological and biochemical pro cesses in human brain in vivo, and has yielded new insights into both normal physiology and diseases (Kuhl et aI. , 1982;Foster, 1983; Wagner et aI. , 1983; Frost et aI., 1985;Phelps and Mazziotta, 1985;Frost, 1986; Yamaguchi et aI. , 1986; Yoshii et aI., Abbreviations used: AU, arbitrary units; FWHM, full width at half-maximum; OM, gray matter; MRI, magnetic resonance im aging; PET, positron emission tomography; RMSE, relative mean-squared error; ROI, region of interest; SPOR, spoiled grass; WM, white matter. 571plied in a test case of temporal lobe epilepsy revealing an increase in radiotracer activity in GM that was undetec ted in the PET image before correction for partial volume effects. In computer simulations, errors in the segmenta tion of GM and errors in registration of PET and MRI images resulted in less than 15% inaccuracy in the GM PET image. In conclusion, GM PET permits accurate de termination of the actual radiotracer concentration in hu man brain GM in vivo. The method differentiates whether a change in the apparent radiotracer concentration re flects solely an alteration in GM volume or rather a change in radiotracer concentration per unit volume of GM. Key Words: Brain gray matter-Positron emission tomography-Magnetic resonance imaging-Partial vol ume effects-Aging-Dementia-Brain atrophy.1988; Fowler, 1990; Frost and Wagner, 1990; Leen ders et aI., 1990;Martin et al., 1991; Mayberg et aI. , 1991). Nevertheless, a limitation of PET remains: its relatively poor spatial resolution. As a result, PET quantification, especially in structures smaller than two times the full width at half-maximum (FWHM) of the tomograph, is affected by partial volume effects (Hoffmann et aI. , 1979). Given that the in-plane FWHM of current PET instruments ranges from 2.6 mm (Valk et aI. , 1990) to about 14 mm, tracer activity in many brain structures, in cluding the neocortex, is often underestimated. In neocortex, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) spaces are convo luted, and cannot be resolved using PET instrumen tation; a cortical PET signal thus reflects the aver age tracer concentr...

Various methodologies for 99m Tc-sestamibi parathyroid scintigraphy are in clinical use. There are few direct comparisons between the different methods and even less evidence supporting the superiority of one over another. Some reports suggest that SPECT is superior to planar imaging. The addition of CT to SPECT may further improve parathyroid adenoma localization. The purpose of our investigation was to compare hybrid SPECT/CT, SPECT, and planar imaging and to determine whether dual-phase imaging is advantageous for the 3 methodologies. Methods: Scintigraphy was performed on 110 patients with primary hyperparathyroidism and no prior neck surgery. Of these, 98 had single adenomas and are the subject of this review. Planar imaging and SPECT/CT were performed at 15 min and 2 h after injection. Six image sets (early and delayed planar imaging, SPECT, and SPECT/CT) and combinations of the 2 image sets were reviewed for adenoma localization at 13 possible sites. Each review was scored for location and certainty of focus by 2 reviewer groups. Surgical location served as the standard. Sensitivity, specificity, area under the curve, positive predictive value, negative predictive value, and k-values were determined for each method. Results: The overall k-coefficient (certainty of adenoma focus) between reading groups was 0.68 (95% confidence interval, 0.66-0.70). The highest values were for dualphase studies that included SPECT/CT. Dual-phase planar imaging, SPECT, and SPECT/CT were statistically significantly superior to single-phase early or delayed imaging in sensitivity, area under the curve, and positive predictive value. Neither single-phase nor dual-phase SPECT was statistically superior to dual-phase planar imaging. Early-phase SPECT/CT in combination with any delayed imaging method was superior to dualphase planar imaging or SPECT for sensitivity, area under the curve, and positive predictive value. Conclusion: Early SPECT/ CT in combination with any delayed imaging method was statistically significantly superior to any single-or dual-phase planar or SPECT study for parathyroid adenoma localization. Localization with dual-phase acquisition was more accurate than with singlephase 99m Tc-sestamibi scintigraphy for planar imaging, SPECT, and SPECT/CT.

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Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted PET imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of F-DCFPyL (2-(3-{1-carboxy-5-[(6-F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) PET examinations in a prospective setting mimicking the typical clinical workflow at a prostate cancer referral center. Four readers (2 experienced readers (ERs,>3 y of PSMA-targeted PET interpretation experience) and 2 inexperienced readers (IRs, <1 y of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 F-DCFPyL PET/CT studies independently. Per scan, a maximum of 5 target lesions was selected by the observers, and a PSMA-RADS score for every target lesion was recorded. No specific preexisting conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated, and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed. The number of target lesions identified by each observer was as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least 2 individual observers (all 4 readers selected the same target lesion in 58 of 125 [46.4%] instances, 3 readers in 40 of 125 [32%], and 2 observers in 27 of 125 [21.6%]). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient [ICC] for 4, 3, and 2 identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC, 0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC, 0.84), with a significant difference for ER (ICC, 0.97) vs. IR (ICC, 0.74) ( = 0.005). PSMA-RADS demonstrated a high concordance rate in this study, even among readers with different levels of experience. This finding suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.

Understanding the distribution of microbicide and human immunodeficiency virus (HIV) within the gastrointestinal tract is critical to development of rectal HIV microbicides. A hydroxyethylcellulose-based microbicide surrogate or viscosity-matched semen surrogate, labeled with gadolinium-DTPA (diethylene triamine pentaacetic acid) and 99mTechnetium-sulfur colloid, was administered to three subjects under varying experimental conditions to evaluate effects of enema, coital simulation, and microbicide or semen simulant over 5 h duration. Quantitative assessment used single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI) imaging, and sigmoidoscopic sampling. Over 4 h, radiolabel migrated cephalad in all studies by a median (interquartile range) of 50% (29-102%; P<0.001), as far as the splenic flexure (approximately 60 cm) in 12% of studies. There was a correlation in concentration profile between endoscopic sampling and SPECT assessments. HIV-sized particles migrate retrograde, 60 cm in some studies, 4 h after simulated ejaculation in our model. SPECT/CT, MRI, and endoscopy can be used quantitatively to facilitate rational development of microbicides for rectal use.

Purpose Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Livermean + [2 × Liversd]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results Of the 32 patients, the majority were male (n = 19, 59%), 65 years or older (n = 21, 66%), and had tumors located in the pancreatic head (n = 27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8months (95% confidence interval [CI], 15.7–22.0). An MTV of 26.8 cm3 or greater (hazard ratio [HR] 4.46, 95% CI 1.64–5.88, P<.003) and TLG of 70.9 or greater (HR3.08,95%CI 1.18–8.02,P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19–22.21, P = .029) and TLG (HR 3.34, 95% CI 1.07–10.48, P = .038) remained independently associated with overall survival in separate multivariate analyses. Conclusions Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in tailoring therapy.

Purpose To determine the diagnostic accuracy of a semiautomated 18F-FDG PET/CT measurement of total lesion glycolysis (TLG), maximum and peak standardized uptake value at lean body mass (SUL-Max and SUL-Peak), qualitative estimates of left/right nodal symmetry and FDG uptake for differentiating lymphoma from reactive adenopathy in HIV-infected patients. Methods We retrospectively analyzed 41 whole-body 18F-FDG PET/CT studies performed in HIV-infected patients for clinical reasons. The study received institutional review board approval. Of the 41 patients, 19 had biopsy-proven untreated lymphoma, and 22 with reactive adenopathy without malignancy on follow-up were used as controls. Nodal and extranodal visual qualitative metabolic scores, SUL-Max, SUL-Peak, CT nodal size, and PERCIST 1.0 threshold-based TLG and metabolic tumor volume (MTV) were determined. The qualitative intensity of nodal involvement and symmetry of uptake were compared using receiver operator curve (ROC) analysis. HIV plasma viral RNA measurements were also obtained. Results All of the quantitative PET metrics performed well in differentiating lymphoma from reactive adenopathy and performed better than qualitative visual intensity scores. The areas under the ROC curves (AUC) were significantly higher for TLG=0.96, single SUL-Peak=0.96, single SUL-Max=0.97, and MTV=0.96, compared to 0.67 for CT nodal size (p<0.001). These PET metrics performed best in separating the two populations in aviremic patients, with AUCs of 1 (AUC 0.91 for CT nodal size). TLG, MTV, SUL-Peak and SUL-Max were more reliable markers among viremic individuals, with AUCs between 0.84 and 0.93, compared to other metrics. PET metrics were significantly correlated with plasma viral load in HIV-reactive adenopathy controls. Asymmetrical FDG uptake had an accuracy of 90.4 % for differentiating lymphoma from reactive adenopathy in HIV-infected patients. Conclusion Quantitative PET metabolic metrics as well as the qualitative assessment of symmetry of nodal uptake appear to be valuable tools for differentiating lymphoma from reactive adenopathy in HIV-infected patients using FDG PET. These parameters appear more robust in aviremic patients.

Rectally applied antiretroviral microbicides for preexposure prophylaxis (PrEP) of HIV infection are currently in development. Since enemas (rectal douches) are commonly used by men who have sex with men prior to receptive anal intercourse, a microbicide enema could enhance PrEP adherence by fitting seamlessly within the usual sexual practices. We assessed the distribution, safety, and acceptability of three enema types-hyperosmolar (Fleet), hypoosmolar (distilled water), and isoosmolar (Normosol-R)-in a crossover design. Nine men received each enema type in random order. Enemas were radiolabeled [ 99m Tc-diethylene triamine pentaacetic acid (DTPA)] to assess enema distribution in the colon using single photon emission computed tomography/ computed tomography (SPECT/CT) imaging. Plasma 99m Tc-DTPA indicated mucosal permeability. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the 99m Tc-DTPA. Acceptability was assessed after each product use and at the end of the study. SPECT/CT imaging showed that the isoosmolar enema had greater proximal colonic distribution (up to the splenic flexure) and greater luminal and colon tissue concentrations of 99m Tc-DTPA when compared to the other enemas ( p < 0.01). Colon biopsies also showed that only the hyperosmolar enema caused sloughing of the colonic epithelium ( p < 0.05). In permeability testing, the hypoosmolar enema had higher plasma 99m Tc-DTPA 24-h area under the concentration-time curve and peak concentration compared to the hyperosmolar and isoosmolar enemas, respectively. Acceptability was generally good with no clear preferences among the three enema types. The isoosmolar enema was superior or similar to the other enemas in all categories and is a good candidate for further development as a rectal microbicide vehicle.