Quantitative Comparison of Prone and Supine PERCIST Measurements in Breast Cancer.

Positron emission tomography (PET) is typically performed in the supine position. However, breast magnetic resonance imaging (MRI) is performed in prone, as this improves visibility of deep breast tissues. With the emergence of hybrid scanners that integrate molecular information from PET and functional information from MRI, it is of great interest to determine if the prognostic utility of prone PET is equivalent to supine. We compared PERCIST (PET Response Criteria in Solid Tumors) measurements between prone and supine FDG-PET in patients with breast cancer and the effect of orientation on predicting pathologic complete response (pCR). In total, 47 patients were enrolled and received up to 6 cycles of neoadjuvant therapy. Prone and supine FDG-PET were performed at baseline (t0 ; n = 46), after cycle 1 (t1 ; n = 1) or 2 (t2 ; n = 10), or after all neoadjuvant therapy (t3 ; n = 19). FDG uptake was quantified by maximum and peak standardized uptake value (SUV) with and without normalization to lean body mass; that is, SUVmax , SUVpeak , SULmax , and SULpeak . PERCIST measurements were performed for each paired baseline and post-treatment scan. Receiver operating characteristic analysis for the prediction of pCR was performed using logistic regression that included age and tumor size as covariates. SUV and SUL metrics were significantly different between orientation (P < .001), but were highly correlated (P > .98). Importantly, no differences were observed with the PERCIST measurements (P > .6). Overlapping 95% confidence intervals for the receiver operating characteristic analysis suggested no difference at predicting pCR. Therefore, prone and supine PERCIST in this data set were not statistically different.

Towards real-time topical detection and characterization of FDG dose infiltration prior to PET imaging.

PURPOSE: To dynamically detect and characterize 18F-fluorodeoxyglucose (FDG) dose infiltrations and evaluate their effects on positron emission tomography (PET) standardized uptake values (SUV) at the injection site and in control tissue. METHODS: Investigational gamma scintillation sensors were topically applied to patients with locally advanced breast cancer scheduled to undergo limited whole-body FDG-PET as part of an ongoing clinical study. Relative to the affected breast, sensors were placed on the contralateral injection arm and ipsilateral control arm during the resting uptake phase prior to each patient's PET scan. Time-activity curves (TACs) from the sensors were integrated at varying intervals (0-10, 0-20, 0-30, 0-40, and 30-40 min) post-FDG and the resulting areas under the curve (AUCs) were compared to SUVs obtained from PET. RESULTS: In cases of infiltration, observed in three sensor recordings (30 %), the injection arm TAC shape varied depending on the extent and severity of infiltration. In two of these cases, TAC characteristics suggested the infiltration was partially resolving prior to image acquisition, although it was still apparent on subsequent PET. Areas under the TAC 0-10 and 0-20 min post-FDG were significantly different in infiltrated versus non-infiltrated cases (Mann-Whitney, p < 0.05). When normalized to control, all TAC integration intervals from the injection arm were significantly correlated with SUVpeak and SUVmax measured over the infiltration site (Spearman ρ ≥ 0.77, p < 0.05). Receiver operating characteristic (ROC) analyses, testing the ability of the first 10 min of post-FDG sensor data to predict infiltration visibility on the ensuing PET, yielded an area under the ROC curve of 0.92. CONCLUSIONS: Topical sensors applied near the injection site provide dynamic information from the time of FDG administration through the uptake period and may be useful in detecting infiltrations regardless of PET image field of view. This dynamic information may also complement the static PET image to better characterize the true extent of infiltrations.

MR Imaging Biomarkers in Oncology Clinical Trials.

The authors discuss eight areas of quantitative MR imaging that are currently used (RECIST, DCE-MR imaging, DSC-MR imaging, diffusion MR imaging) in clinical trials or emerging (CEST, elastography, hyperpolarized MR imaging, multiparameter MR imaging) as promising techniques in diagnosing cancer and assessing or predicting response of cancer to therapy. Illustrative applications of the techniques in the clinical setting are summarized before describing the current limitations of the methods.

Comparison of prone versus supine 18F-FDG-PET of locally advanced breast cancer: Phantom and preliminary clinical studies.

PURPOSE: Previous studies have demonstrated how imaging of the breast with patients lying prone using a supportive positioning device markedly facilitates longitudinal and/or multimodal image registration. In this contribution, the authors' primary objective was to determine if there are differences in the standardized uptake value (SUV) derived from [(18)F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in breast tumors imaged in the standard supine position and in the prone position using a specialized positioning device. METHODS: A custom positioning device was constructed to allow for breast scanning in the prone position. Rigid and nonrigid phantom studies evaluated differences in prone and supine PET. Clinical studies comprised 18F-FDG-PET of 34 patients with locally advanced breast cancer imaged in the prone position (with the custom support) followed by imaging in the supine position (without the support). Mean and maximum values (SUVpeak and SUVmax, respectively) were obtained from tumor regions-of-interest for both positions. Prone and supine SUV were linearly corrected to account for the differences in 18F-FDG uptake time. Correlation, Bland-Altman, and nonparametric analyses were performed on uptake time-corrected and uncorrected data. RESULTS: SUV from the rigid PET breast phantom imaged in the prone position with the support device was 1.9% lower than without the support device. In the nonrigid PET breast phantom, prone SUV with the support device was 5.0% lower than supine SUV without the support device. In patients, the median (range) difference in uptake time between prone and supine scans was 16.4 min (13.4-30.9 min), which was significantly-but not completely-reduced by the linear correction method. SUVpeak and SUVmax from prone versus supine scans were highly correlated, with concordance correlation coefficients of 0.91 and 0.90, respectively. Prone SUVpeak and SUVmax were significantly lower than supine in both original and uptake time-adjusted data across a range of index times (P < < 0.0001, Wilcoxon signed rank test). Before correcting for uptake time differences, Bland-Altman analyses revealed proportional bias between prone and supine measurements (SUVpeak and SUVmax) that increased with higher levels of FDG uptake. After uptake time correction, this bias was significantly reduced (P < 0.01). Significant prone-supine differences, with regard to the spatial distribution of lesions relative to isocenter, were observed between the two scan positions, but this was poorly correlated with the residual (uptake time-corrected) prone-supine SUVpeak difference (P = 0.78). CONCLUSIONS: Quantitative 18F-FDG-PET/CT of the breast in the prone position is not deleteriously affected by the support device but yields SUV that is consistently lower than those obtained in the standard supine position. SUV differences between scans arising from FDG uptake time differences can be substantially reduced, but not removed entirely, with the current correction method. SUV from the two scan orientations is quantitatively different and should not be assumed equivalent or interchangeable within the same subject. These findings have clinical relevance in that they underscore the importance of patient positioning while scanning as a clinical variable that must be accounted for with longitudinal PET measurement, for example, in the assessment of treatment response.

Longitudinal, intermodality registration of quantitative breast PET and MRI data acquired before and during neoadjuvant chemotherapy: preliminary results.

PURPOSE: The authors propose a method whereby serially acquired DCE-MRI, DW-MRI, and FDG-PET breast data sets can be spatially and temporally coregistered to enable the comparison of changes in parameter maps at the voxel level. METHODS: First, the authors aligned the PET and MR images at each time point rigidly and nonrigidly. To register the MR images longitudinally, the authors extended a nonrigid registration algorithm by including a tumor volume-preserving constraint in the cost function. After the PET images were aligned to the MR images at each time point, the authors then used the transformation obtained from the longitudinal registration of the MRI volumes to register the PET images longitudinally. The authors tested this approach on ten breast cancer patients by calculating a modified Dice similarity of tumor size between the PET and MR images as well as the bending energy and changes in the tumor volume after the application of the registration algorithm. RESULTS: The median of the modified Dice in the registered PET and DCE-MRI data was 0.92. For the longitudinal registration, the median tumor volume change was -0.03% for the constrained algorithm, compared to -32.16% for the unconstrained registration algorithms (p = 8 × 10(-6)). The medians of the bending energy were 0.0092 and 0.0001 for the unconstrained and constrained algorithms, respectively (p = 2.84 × 10(-7)). CONCLUSIONS: The results indicate that the proposed method can accurately spatially align DCE-MRI, DW-MRI, and FDG-PET breast images acquired at different time points during therapy while preventing the tumor from being substantially distorted or compressed.

Amide proton transfer imaging of the human breast at 7T: development and reproducibility.

Chemical exchange saturation transfer (CEST) can offer information about protons associated with mobile proteins through the amide proton transfer (APT) effect, which has been shown to discriminate tumor from healthy tissue and, more recently, has been suggested as a prognosticator of response to therapy. Despite this promise, APT effects are small (only a few percent of the total signal), and APT imaging is often prone to artifacts resulting from system instability. Here we present a procedure that enables the detection of APT effects in the human breast at 7T while mitigating these issues. Adequate signal-to-noise ratio (SNR) was achieved via an optimized quadrature RF breast coil and 3D acquisitions. To reduce the influence of fat, effective fat suppression schemes were developed that did not degrade SNR. To reduce the levels of ghosting artifacts, dummy scans have been integrated into the scanning protocol. Compared with results obtained at 3T, the standard deviation of the measured APT effect was reduced by a factor of four at 7T, allowing for the detection of APT effects with a standard deviation of 1% in the human breast at 7T. Together, these results demonstrate that the APT effect can be reliably detected in the healthy human breast with a high level of precision at 7T.

Hypoinsulinemia regulates amphetamine-induced reverse transport of dopamine.

The behavioral effects of psychomotor stimulants such as amphetamine (AMPH) arise from their ability to elicit increases in extracellular dopamine (DA). These AMPH-induced increases are achieved by DA transporter (DAT)-mediated transmitter efflux. Recently, we have shown that AMPH self-administration is reduced in rats that have been depleted of insulin with the diabetogenic agent streptozotocin (STZ). In vitro studies suggest that hypoinsulinemia may regulate the actions of AMPH by inhibiting the insulin downstream effectors phosphotidylinositol 3-kinase (PI3K) and protein kinase B (PKB, or Akt), which we have previously shown are able to fine-tune DAT cell-surface expression. Here, we demonstrate that striatal Akt function, as well as DAT cell-surface expression, are significantly reduced by STZ. In addition, our data show that the release of DA, determined by high-speed chronoamperometry (HSCA) in the striatum, in response to AMPH, is severely impaired in these insulin-deficient rats. Importantly, selective inhibition of PI3K with LY294002 within the striatum results in a profound reduction in the subsequent potential for AMPH to evoke DA efflux. Consistent with our biochemical and in vivo electrochemical data, findings from functional magnetic resonance imaging experiments reveal that the ability of AMPH to elicit positive blood oxygen level-dependent signal changes in the striatum is significantly blunted in STZ-treated rats. Finally, local infusion of insulin into the striatum of STZ-treated animals significantly recovers the ability of AMPH to stimulate DA release as measured by high-speed chronoamperometry. The present studies establish that PI3K signaling regulates the neurochemical actions of AMPH-like psychomotor stimulants. These data suggest that insulin signaling pathways may represent a novel mechanism for regulating DA transmission, one which may be targeted for the treatment of AMPH abuse and potentially other dopaminergic disorders.