The NMR hyperpolarization of uniformly 15 N-labeled [ 15 N 3 ]metronidazole is demonstrated by using SABRE-SHEATH. In this antibiotic, the 15 NO 2 group is hyperpolarized throughs pin relays createdb y 15 Ns pins in [ 15 N 3 ]metronidazole, and the polarization is transferred from parahydrogen-derivedh ydrides over six chemical bonds. In less than am inute of parahydrogen bubbling at approximately 0.4 mT, ah igh level of nuclear spin polarization( P 15N ) of around 16 %i sa chieved on all three 15 Ns ites. This prod-uct of 15 Np olarization andc oncentration of 15 Ns pins is arounds ix-fold bettert han any previous value determined for 15 NS ABRE-derived hyperpolarization. At 1.4 T, the hyperpolarized state persists fort ens of minutes (relaxation time, T 1 %10 min). An ovel synthesis of uniformly 15 N-enriched metronidazole is reported with ay ield of 15 %. This approachc an potentially be used for synthesis of aw ide variety of in vivom etabolic probesw ith potentialu ses ranging from hypoxiasensing to theranostic imaging.[a] Prof.

BackgroundSemiquantitative methods such as the standardized uptake value ratio (SUVR) require normalization of the radiotracer activity to a reference tissue to monitor changes in the accumulation of amyloid-β (Aβ) plaques measured with positron emission tomography (PET). The objective of this study was to evaluate the effect of reference tissue normalization in a test–retest 18F-florbetapir SUVR study using cerebellar gray matter, white matter (two different segmentation masks), brainstem, and corpus callosum as reference regions.MethodsWe calculated the correlation between 18F-florbetapir PET and concurrent cerebrospinal fluid (CSF) Aβ1–42 levels in a late mild cognitive impairment cohort with longitudinal PET and CSF data over the course of 2 years. In addition to conventional SUVR analysis using mean and median values of normalized brain radiotracer activity, we investigated a new image analysis technique—the weighted two-point correlation function (wS2)—to capture potentially more subtle changes in Aβ-PET data.ResultsCompared with the SUVRs normalized to cerebellar gray matter, all cerebral-to-white matter normalization schemes resulted in a higher inverse correlation between PET and CSF Aβ1–42, while the brainstem normalization gave the best results (high and most stable correlation). Compared with the SUVR mean and median values, the wS2 values were associated with the lowest coefficient of variation and highest inverse correlation to CSF Aβ1–42 levels across all time points and reference regions, including the cerebellar gray matter.ConclusionsThe selection of reference tissue for normalization and the choice of image analysis method can affect changes in cortical 18F-florbetapir uptake in longitudinal studies.

Depression is associated with markers of accelerated aging, but it is unclear how this relationship changes across the lifespan. We examined whether a brain-based measure of accelerated aging differed between depressed and never-depressed subjects across the adult lifespan and whether it was related to cognitive performance and disability. We applied a machine-learning approach that estimated brain age from structural MRI data in two depressed cohorts, respectively 170 midlife adults and 154 older adults enrolled in studies with common entry criteria. Both cohorts completed broad cognitive batteries and the older subgroup completed a disability assessment. The machine-learning model estimated brain age from MRI data, which was compared to chronological age to determine the brain–age gap (BAG; estimated age-chronological age). BAG did not differ between midlife depressed and nondepressed adults. Older depressed adults exhibited significantly higher BAG than nondepressed elders (Wald χ2 = 8.84, p = 0.0029), indicating a higher estimated brain age than chronological age. BAG was not associated with midlife cognitive performance. In the older cohort, higher BAG was associated with poorer episodic memory performance (Wald χ2 = 4.10, p = 0.0430) and, in the older depressed group alone, slower processing speed (Wald χ2 = 4.43, p = 0.0354). We also observed a statistical interaction where greater depressive symptom severity in context of higher BAG was associated with poorer executive function (Wald χ2 = 5.89, p = 0.0152) and working memory performance (Wald χ2 = 4.47, p = 0.0346). Increased BAG was associated with greater disability (Wald χ2 = 6.00, p = 0.0143). Unlike midlife depression, geriatric depression exhibits accelerated brain aging, which in turn is associated with cognitive and functional deficits.

Evaluating the symptomatic progression of mild cognitive impairment (MCI) caused by Alzheimer disease (AD) is practically accomplished by tracking performance on cognitive tasks, such as the Alzheimer Disease Assessment Scale’s cognitive subscale (ADAS_cog), the Mini-Mental Status Examination (MMSE), and the Functional Activities Questionnaire (FAQ). The longitudinal relationships between cognitive decline and metabolic function as assessed using 18F-FDG PET are needed to address both the cognitive and the biologic progression of disease state in individual subjects. We conducted an exploratory investigation to evaluate longitudinal changes in brain glucose metabolism of individual subjects and their relationship to the subject’s changes of cognitive status. Methods We describe a method to determine correlations in 18F-FDG spatial distribution over time. This parameter is termed the regional 18F-FDG time correlation coefficient (rFTC). By using linear mixed-effects models, we determined the difference in the rFTC decline rate between controls and subjects at high risk of developing AD, such as individuals with MCI or the presence of apolipoprotein E (APOE)–ε4 allele. The association between each subject’s rFTC and performance on cognitive tests (ADAS_cog, MMSE, and FAQ) was determined with 2 different correlation methods. All subject data were downloaded from the Alzheimer Disease Neuroimaging Initiative. Results The rFTC values of controls remained fairly constant over time (−0.003 annual change; 95% confidence interval, −0.010– 0.004). In MCI patients, the rFTC declined faster than in controls by an additional annual change of −0.02 (95% confidence interval, −0.030 to −0.010). In MCI patients, the decline in rFTC was associated with cognitive decline (ADAS_cog, P = 0.011; FAQ, P = 0.0016; MMSE, P = 0.004). After a linear effect of time was accounted for, visit-to-visit changes in rFTC correlated with visit-to-visit changes in all 3 cognitive tests. Conclusion Longitudinal changes in rFTC detect subtle metabolic changes in individuals associated with variations in their cognition. This analytic tool may be useful for a patient-based monitoring of cognitive decline.

Anesthesia is currently required for positron emission tomography (PET) studies of the animal brain in order to eliminate motion artifacts. However, anesthesia profoundly affects the neurological state of the animal, complicating the interpretation of PET data. Furthermore, it precludes the use of PET to study the brain during normal behavior. The rat conscious animal PET tomograph (RatCAP) is designed to eliminate the need for anesthesia in rat brain studies. It is a miniaturized full-ring PET scanner that is attached directly to the head, imaging nearly the entire brain. RatCAP utilizes arrays of 2 mm 2 mm LSO crystals coupled to matching avalanche photodiode arrays, which are in turn read out by full custom integrated circuits. Principal challenges have been addressed considering the physical constraints on size, weight, and heat generation in addition to the usual requirements of small-animal PET, such as high spatial resolution in the presence of parallax error. A partial prototype has been constructed and preliminary measurements and optimization completed. Realistic Monte Carlo simulations have also been carried out to optimize system performance, which is predicted to be competitive with existing microPET systems.Index Terms-Biomedical applications of nuclear radiation, biomedical nuclear imaging, gamma-ray detectors, motion compensation, nervous system, positron emission tomography (PET).

Introduction We examined networks of tau connectivity between brain regions based on correlations of their [18F]flortaucipir positron emission tomography (PET) uptake to evaluate sex‐specific differences in brain‐wide tau propagation. Methods PET data of clinically normal and mild cognitive impairment (MCI) subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used to examine differences in network architectures across the groups. Results The tau‐based network architecture resembled progression of tauopathy from Braak stage I to VI regions. Compared to men, women had higher network density and an increased number of direct regional connections in co‐occurrence with increased brain‐wide tau burden, particularly at MCI. Several regions, including superior parietal lobe and parahippocampus served as connecting bridges between communities at different Braak stages. Discussion Network characteristics in women may favor an accelerated brain‐wide tau spread leading to a higher tau burden in women than men with MCI with implications for the greater female preponderance in Alzheimer's disease diagnosis.

Rationale Current radiological methods for diagnosing breast cancer detect specific morphological features of solid tumors and/or any associated calcium deposits. These deposits originate from an early molecular microcalcification process which consists of two types: type 1 is calcium oxylate (CO) and type II is carbonated calcium hydroxyapetite (HAP). Type I microcalcifications are mainly associated with benign tumors while type II have been shown to be produced, internally, by malignant cells. No current non-invasive in vivo techniques are available for detecting intratumoral microcalcifications. Such a technique would have a significant impact on breast cancer diagnosis and prognosis in preclinical and clinical settings. 18F-NaF PET has been solely used for bone imaging by targeting the bone HAP. In this work, we provide preliminary evidence that 18F-NaF PET imaging can be used to detect breast cancer by targeting the HAP lattice within the tumor microenvironment with high specificity and soft-tissue contrast-to-background ratio, while delineating tumors from inflammation. METHODS Mice were injected with approximately 106 MDA-MB-231 cells subcutaneously and imaged with 18F-NaF PET/CT in a 120 min dynamic sequence when the tumors reached a size of ~250 mm3. Regions-of-interest (ROIs) were drawn around the tumor, muscle, and bone. The concentration of the radiotracer within those ROIs were compared to one another. For comparison to inflammation, rats with inflammatory paws were subjected to 18F-NaF PET imaging. RESULTS Tumor uptake of 18F− was significantly higher (p<0.05) than muscle uptake where the tumor-to-muscle ratio was ~3.5. The presence of type II microcalcification in the MDA-MB-231 cell line was confirmed histologically using alizarin red S and von Kossa staining as well as Raman microspectroscopy. No uptake of 18F− was observed in the rat inflamed tissue. Lack of HAP in the inflamed tissue was verified histologically. CONCLUSIONS This study provides preliminary evidence suggesting that specific targeting of the HAP within the tumor microenvironment with 18F may be able to distinguishing between inflammation and cancer.

We have designed a multi-pinhole collimator for a dual-headed, stationary SPECT system that incorporates high-resolution silicon double-sided strip detectors. The compact camera design of our system enables imaging at source-collimator distances between 20 and 30 mm. Our analytical calculations show that using knife-edge pinholes with small-opening angles or cylindrically shaped pinholes in a focused, multi-pinhole configuration in combination with this camera geometry can generate narrow sensitivity profiles across the field of view that can be useful for imaging small objects at high sensitivity and resolution. The current prototype system uses two collimators each containing 127 cylindrically shaped pinholes that are focused toward a target volume. Our goal is imaging objects such as a mouse brain, which could find potential applications in molecular imaging.