We present an initial evaluation of a mechanically-cooled, high-purity germanium double-sided strip detector as a potential gamma camera for small-animal SPECT. It is 90 mm in diameter and 10 mm thick with two sets of 16 orthogonal strips that have a 4.5 mm width with a 5 mm pitch. We found an energy resolution of 0.96% at 140 keV, an intrinsic efficiency of 43.3% at 122 keV and a FWHM spatial resolution of approximately 1.5 mm. We demonstrated depth-of-interaction estimation capability through comparison of pinhole acquisitions with a point source on and off axis. Finally, a flood-corrected-flood image exhibited a strip-level uniformity of less than 1%. This high-purity germanium offers many desirable properties for small-animal SPECT.

ObjectivesSemi-quantitative image analysis methods in Alzheimer’s Disease (AD) require normalization of positron emission tomography (PET) images. However, recent studies have found variabilities associated with reference region selection of amyloid PET images. Haralick features (HFs) generated from the Gray Level Co-occurrence Matrix (GLCM) quantify spatial characteristics of amyloid PET radiotracer uptake without the need for intensity normalization. The objective of this study is to calculate several HFs in different diagnostic groups and determine the group differences.MethodsAll image and metadata were acquired through the Alzheimer’s Disease Neuroimaging Initiative database. Subjects were grouped in three ways: by clinical diagnosis, by APOE e4 allele, and by Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) score. Several GLCM matrices were calculated for different direction and distances (1–4 mm) from multiple regions on PET images. The HFs, contrast, correlation, dissimilarity, energy, entropy, and homogeneity, were calculated from these GLCMs. Wilcoxon tests and Student t-tests were performed on Haralick features and standardized uptake value ratio (SUVR) values, respectively, to determine group differences. In addition to statistical testing, receiver operating characteristic (ROC) curves were generated to determine the discrimination performance of the selected regional HFs and the SUVR values.ResultsPreliminary results from statistical testing indicate that HFs were capable of distinguishing groups at baseline and follow-up (false discovery rate corrected p<0.05) in particular regions at much higher occurrences than SUVR (81 of 252). Conversely, we observed nearly no significant differences between all groups within ROIs at baseline or follow-up utilizing SUVR. From the ROC analysis, we found that the Energy and Entropy offered the best performance to distinguish Normal versus mild cognitive impairment and ADAS-Cog negative versus ADAS-Cog positive groups.ConclusionThese results suggest that this technique could improve subject stratification in AD drug trials and help to evaluate the disease progression and treatment effects longitudinally without the disadvantages associated with intensity normalization.

Recent Alzheimer’s trials have recruited cognitively normal people at risk for Alzheimer’s dementia. Due to the lack of clinical symptoms in normal population, conventional clinical outcome measures are not suitable for these early trials. While several groups are developing new composite cognitive tests that could serve as potential outcome measures by detecting subtle cognitive changes in normal people, there is a need for longitudinal brain imaging techniques that can correlate with temporal changes in these new tests and provide additional objective measures of neuropathological changes in brain. Positron emission tomography (PET) is a nuclear medicine imaging procedure based on the measurement of annihilation photons after positron emission from radiolabeled molecules that allow tracking of biological processes in body, including the brain. PET is a well-established in vivo imaging modality in Alzheimer’s disease diagnosis and research due to its capability of detecting abnormalities in three major hallmarks of this disease. These include 1) amyloid beta plaques, 2) neurofibrillary tau tangles and 3) decrease in neuronal activity due to loss of nerve cell connection and death. While semi-quantitative PET imaging techniques are commonly used to set discrete cut-points to stratify abnormal levels of amyloid accumulation and neurodegeneration, they are sub-optimal for detecting subtle longitudinal changes. In this study, we have identified and discussed four critical barriers in conventional longitudinal PET imaging that may be particularly relevant for early Alzheimer’s disease studies. These include within and across subject heterogeneity of AD-affected brain regions, PET intensity normalization, neuronal compensations in early disease stages and cerebrovascular amyloid deposition.

We present an initial evaluation of a mechanically cooled, high-purity germanium double-sided strip detector as a potential gamma camera for small-animal SPECT. It is 90 mm in diameter and 10 mm thick with two sets of 16 orthogonal strips that have a 4.75 mm width with a 5 mm pitch. A sub-strip interpolation method is used to bin the data at a pixel size of 0.53mm x 0.53mm, while it is also possible to estimate the depth of interaction based on CFD time differences between the anode and cathode. The system has an energy resolution of 0.92% at 140 keY and an intrinsic efficiency of 55.40% at 122 keY.Simulations suggest that increases in the efficiency should be possible by altering signal processing to include Compton events in which charge is collected on more than one strip. Integral uniformity in the central field of view for strips was found to be less than 1 % in a flood-corrected flood while pixel-level uniformity was 2.98%. Due to the excellent energy resolution, the presence of a scattering medium did not greatly alter the FWHM or FWTM of a pinhole projection when compared to an acquisition without a scattering medium. This high-purity germanium system offers many desirable properties for small animal SPECT.

We conducted simulations to compare the potential imaging performance for breast cancer detection with High-Purity Germanium (HPGe) and Cadmium Zinc Telluride (CZT) systems with 1% and 3.8% energy resolution at 140 keV, respectively. Using the Monte Carlo N-Particle (MCNP5) simulation package, we modelled both 5 mm-thick CZT and 10 mm-thick HPGe detectors with the same parallel-hole collimator for the imaging of a breast/torso phantom. Simulated energy spectra were generated, and planar images were created for various energy windows around the 140-keV photopeak. Relative sensitivity and scatter and the torso fractions were calculated along with tumour contrast and signal-to-noise ratios (SNR). Simulations showed that utilizing a ±1.25% energy window with an HPGe system better suppressed torso background and small-angle scattered photons than a comparable CZT system using a −5%/+10% energy window. Both systems provided statistically similar contrast and SNR, with HPGe providing higher relative sensitivity. Lowering the counts of HPGe images to match CZT count density still yielded equivalent contrast between HPGe and CZT. Thus, an HPGe system may provide equivalent breast imaging capability at lower injected radioactivity levels when acquiring for equal imaging time.

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