Partial Volume Correction Research Articles

Relationship between type 1 metabotropic glutamate receptors and cerebellar ataxia.

Imaging of type 1 metabotropic glutamate receptor (mGluR1) has recently become possible using positron emission tomography (PET). We aimed to examine the relationship between mGluR1 and cerebellar ataxia. Families with spinocerebellar ataxia type 19/22 (SCA19/22) and SCA6, six patients with sporadic SCA, and 26 healthy subjects underwent PET using an mGluR1 radiotracer. Volumes-of-interest were placed on the anterior and posterior lobes and vermis. The binding potential (BPND) was calculated to estimate mGluR1 availability. A partial volume correction was applied to the BPND values. The Scale for the Assessment and Rating of Ataxia (SARA) score were measured. In each patient with SCA19/22 and SCA6, the anterior lobe showed the highest decrease rates in the BPND values, compared with healthy subjects. In the families with SCA19/22 and SCA6, the disease durations and SARA scores were shorter and lower, respectively, in the offspring, compared with the parents. However, the offspring paradoxically showed lower BPND values, especially in the anterior lobe, compared with the parents. The patients with sporadic SCA showed significantly lower BPND values in all subregions than healthy subjects. The BPND values significantly correlated with the SARA scores in all participants. In conclusion, these results showed a decrease in mGluR1 availability in patients with hereditary and sporadic SCA, a correlation between mGluR1 availability and degree of cerebellar ataxia, and paradoxical findings in two families. These results suggest the potential use of mGluR1 imaging as a specific biomarker of cerebellar ataxia.

Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer's disease.

The cannabinoid type 2 receptor (CB2R) is expressed by immune cells such as monocytes and macrophages. In the brain, CB2R is primarily found on microglia. CB2R upregulation has been reported in animal models of Alzheimer's disease, with a preferential localization near amyloid beta (Aβ) plaques, and in patients post mortem. We performed in vivo brain imaging and kinetic modelling of the CB2R tracer [11C]NE40 in healthy controls (HC) and in patients with Alzheimer's disease (AD) to investigate whether higher CB2R availability regionally colocalized to Aβ deposits is present in vivo. Dynamic 90-min [11C]NE40 PET scans were performed in eight HC and nineAD patients with full kinetic modelling using arterial sampling and metabolite correction and partial volume correction. All AD patients received a static [11C]PIB scan 40min after injection. In four HC, a retest scan with [11C]NE40 PET was performed within 9weeks to investigate test-retest characteristics. [11C]NE40 was metabolized quickly leading to 50% of intact tracer 20min after injection and 20% at 90min. A two-tissue kinetic model fitted most of the time-activity curves best; both binding potential (BPND) and distribution volume (V T) parameters could be used. Brain uptake was generally low with an average K 1 value of 0.07ml/min/ml tissue. V T and BPND were in the range of 0.7-1.8 and 0.6-1.6, respectively. Test values in HC were about 30% for V T and BPND. AD patients showed overall significantly lower CB2R binding. No relationship was found between regional or global amyloid load and CB2R availability. Kinetic modelling of [11C]NE40 is possible with a two-tissue reversible model. In contrast to preclinical and post-mortem data, [11C]NE40 PET shows lower CB2R availability in vivo in AD patients, with no relationship to Aβ plaques. A possible explanation for these findings is that [11C]NE40 binds to CB2R with lower affinity and/or selectivity than to CB1R.

The feasibility of 11C‐PIB‐PET/CT for amyloid plaque burden: validation of the effectiveness of CT‐based partial volume correction

IntroductionAmyloid positron‐emission tomography (PET) imaging with 11C‐Pittsburgh compound B (PiB) is an effective tool for assessing brain amyloid deposits. PET imaging, however, can suffer from the partial volume effect (PVE). PVE has been corrected using MRI (magnetic resonance imaging) image data. However, correction of the PVE of PET using MRI usually requires two separate procedures, imposing a burden on patients and leading to low throughput and inefficient diagnoses. The advent of PET/computed tomography (PET/CT) may potentially overcome these problems and offer higher throughput and reliable quantification of amyloid plaques and assessment of Alzheimer disease (AD).MethodsWe investigated the feasibility of correcting PVE in amyloid PET using CT, obtained by PET/CT, instead of MRI. We demonstrated the efficacy of partial volume correction (PVC) based on CT by comparing the results of CT‐based PVC and those of MRI‐based PVC using images acquired from AD patients and controls.ResultsBoth methods were able to perform PVC. Slight but significant differences between standard uptake volume ratio (SUVR) values were noted between the two modalities; these were attenuated by constant multiplication.Conclusion CT will potentially replace MRI for PVC, allowing the use of a single PET/CT scanner for amyloid plaque quantitation.

Optimization of yttrium-90 PET for simultaneous PET/MR imaging: A phantom study.

Positron emission tomography (PET) imaging of yttrium-90 in the liver post radioembolization has been shown useful for personalized dosimetry calculations and evaluation of extrahepatic deposition. The purpose of this study was to quantify the benefits of several MR-based data correction approaches offered by using a combined PET/MR system to improve Y-90 PET imaging. In particular, the feasibility of motion and partial volume corrections were investigated in a controlled phantom study. The ACR phantom was filled with an initial concentration of 8 GBq of Y-90 solution resulting in a contrast of 10:1 between the hot cylinders and the background. Y-90 PET motion correction through motion estimates from MR navigators was evaluated by using a custom-built motion stage that simulated realistic amplitudes of respiration-induced liver motion. Finally, the feasibility of an MR-based partial volume correction method was evaluated using a wavelet decomposition approach. Motion resulted in a large (∼40%) loss of contrast recovery for the 8 mm cylinder in the phantom, but was corrected for after MR-based motion correction was applied. Partial volume correction improved contrast recovery by 13% for the 8 mm cylinder. MR-based data correction improves Y-90 PET imaging on simultaneous PET/MR systems. Assessment of these methods must be studied further in the clinical setting.

Estimation of an image derived input function with MR-defined carotid arteries in FDG-PET human studies using a novel partial volume correction method

Kinetic analysis of 18F-fluorodeoxyglucose positron emission tomography data requires an accurate knowledge the arterial input function. The gold standard method to measure the arterial input function requires collection of arterial blood samples and is an invasive method. Measuring an image derived input function is a non-invasive alternative but is challenging due to partial volume effects caused by the limited spatial resolution of the positron emission tomography scanners. In this work, a practical image derived input function extraction method is presented, which only requires segmentation of the carotid arteries from MR images. The simulation study results showed that at least 92% of the true intensity could be recovered after the partial volume correction. Results from 19 subjects showed that the mean cerebral metabolic rate of glucose calculated using arterial samples and partial volume corrected image derived input function were 26.9 and 25.4 mg/min/100 g, respectively, for the grey matter and 7.2 and 6.7 mg/min/100 g for the white matter. No significant difference in the estimated cerebral metabolic rate of glucose values was observed between arterial samples and corrected image derived input function (p > 0.12 for grey matter and white matter). Hence, the presented image derived input function extraction method can be a practical alternative to noninvasively analyze dynamic 18F-fluorodeoxyglucose data without the need for blood sampling.

Lower cerebral blood flow is associated with faster cognitive decline in Alzheimer\u2019s disease

ObjectiveTo determine whether lower cerebral blood flow (CBF) is associated with faster cognitive decline in patients with Alzheimer’s disease (AD).MethodsWe included 88 patients with dementia due to AD from the Amsterdam Dementia Cohort. Mean follow-up was 2 ± 1 years. Linear mixed models were used to determine associations of lower whole brain and regional pseudo-continuous arterial spin labelling measured CBF with rate of cognitive decline as measured with repeated mini-mental state examination (MMSE). Model 1 was adjusted for age, sex, and education. Model 2 was additionally adjusted for normalized gray matter volume, medial temporal lobe atrophy, white matter hyperintensities, microbleeds, and lacunes. Analyses were repeated after partial volume correction (PVC) of CBF. Statistical significance was set at p ≤ 0.05.ResultsPatients were 65 ± 7 years old, 44 (50 %) were women, and mean baseline MMSE was 22 ± 4. Annual decline (β[SE]) on the MMSE was estimated at -2.11 (0.25) points per year. Lower whole brain (β[SE]-0.50[0.25]; p ≤ 0.05) and parietal (β[SE]-0.59[0.25]; p < 0.05) CBF were associated with faster cognitive decline. PVC cortical CBF was not associated with cognitive decline.ConclusionsLower CBF, in particular in the posterior brain regions, may have value as a prognostic marker for rate of cognitive decline in AD.Key points• In AD, lower CBF is associated with more rapid cognitive decline.• Decreasing CBF does not reach a plateau early in AD.• PcASL-CFB has additive value to conventional structural MRI measures in AD.

A linear mixed perfusion model for tissue partial volume correction of perfusion estimates in dynamic susceptibility contrast MRI: Impact on absolute quantification, repeatability, and agreement with pseudo-continuous arterial spin labeling

The partial volume effect (PVE) is an important source of bias in brain perfusion measurements. The impact of tissue PVEs in perfusion measurements with dynamic susceptibility contrast MRI (DSC-MRI) has not yet been well established. The purpose of this study was to suggest a partial volume correction (PVC) approach for DSC-MRI and to study how PVC affects DSC-MRI perfusion results. A linear mixed perfusion model for DSC-MRI was derived and evaluated by way of simulations. Twenty healthy volunteers were scanned twice, including DSC-MRI, arterial spin labeling (ASL), and partial volume measurements. Two different algorithms for PVC were employed and assessed. Simulations showed that the derived model had a tendency to overestimate perfusion values in voxels with high fractions of cerebrospinal fluid. PVC reduced the tissue volume dependence of DSC-MRI perfusion values from 44.4% to 4.2% in gray matter and from 55.3% to 14.2% in white matter. One PVC method significantly improved the voxel-wise repeatability, but PVC did not improve the spatial agreement between DSC-MRI and ASL perfusion maps. Significant PVEs were found for DSC-MRI perfusion estimates, and PVC successfully reduced those effects. The findings suggest that PVC might be an important consideration for DSC-MRI applications. Magn Reson Med 77:2203-2214, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Lesion quantification and detection in myocardial (18)F-FDG PET using edge-preserving priors and anatomical information from CT and MRI: a simulation study.

BackgroundThe limited spatial resolution of the clinical PET scanners results in image blurring and does not allow for accurate quantification of very thin or small structures (known as partial volume effect). In cardiac imaging, clinically relevant questions, e.g. to accurately define the extent or the residual metabolic activity of scarred myocardial tissue, could benefit from partial volume correction (PVC) techniques.The use of high-resolution anatomical information for improved reconstruction of the PET datasets has been successfully applied in other anatomical regions. However, several concerns linked to the use of any kind of anatomical information for PVC on cardiac datasets arise. The moving nature of the heart, coupled with the possibly non-simultaneous acquisition of the anatomical and the activity datasets, is likely to introduce discrepancies between the PET and the anatomical image, that in turn might mislead lesion quantification and detection. Non-anatomical (edge-preserving) priors could represent a viable alternative for PVC in this case.In this work, we investigate and compare the regularizing effect of different anatomical and non-anatomical priors applied during maximum-a-posteriori (MAP) reconstruction of cardiac PET datasets. The focus of this paper is on accurate quantification and lesion detection in myocardial 18F-FDG PET.MethodsSimulated datasets, obtained with the XCAT software, are reconstructed with different algorithms and are quantitatively analysed.ResultsThe results of this simulation study show a superiority of the anatomical prior when an ideal, perfectly matching anatomy is used. The anatomical information must clearly differentiate between normal and scarred myocardial tissue for the PVC to be successful. In case of mismatched or missing anatomical information, the quality of the anatomy-based MAP reconstructions decreases, affecting both overall image quality and lesion quantification. The edge-preserving priors produce reconstructions with good noise properties and recovery of activity, with the advantage of not relying on an external, additional scan for anatomy.ConclusionsThe performance of edge-preserving priors is acceptable but inferior to those of a well-applied anatomical prior that differentiates between lesion and normal tissue, in the detection and quantification of a lesion in the reconstructed images. When considering bull’s eye plots, all of the tested MAP algorithms produced comparable results.

Accuracy and Precision of Partial-Volume Correction in Oncological PET/CT Studies.

Four image-based PVC methods and resolution modeling (applied as PVC) were used in combination with several common VOI methods. Performance was evaluated using simulations, phantom experiments, and clinical repeatability studies. Simulations were based on a whole-body 18F-FDG PET scan in which differently sized spheres were placed in lung and mediastinum. A National Electrical Manufacturers Association NU2 quality phantom was used for the experiments. Repeatability data consisted of an 18F-FDG PET/CT study on 11 patients with advanced non-small cell lung cancer and an 18F-fluoromethylcholine PET/CT study on 12 patients with metastatic prostate cancer. Phantom data demonstrated that most PVC methods were strongly affected by the applied resolution kernel, with accuracy differing by about 20%-50% between full-width-at-half-maximum settings of 5.0 and 7.5 mm. For all PVC methods, large differences in accuracy were seen among all VOI methods. Additionally, the image-based PVC methods were observed to have variable sensitivity to the accuracy of the VOI methods. For most PVC methods, accuracy was strongly affected by more than a 2.5-mm misalignment of true (simulated) VOI. When the optimal VOI method for each PVC method was used, high accuracy could be achieved. For example, resolution modeling for mediastinal lesions and iterative deconvolution for lung lesions were 99% ± 1.5% and 99% ± 0.9% accurate, respectively, for spheres 15-40 mm in diameter. Precision worsened slightly for resolution modeling and to a larger extent for some image-based PVC methods. Uncertainties in delineation propagated into uncertainties in PVC performance, as confirmed by the clinical data. The accuracy and precision of the tested PVC methods depended strongly on VOI method, resolution settings, contrast, and spatial alignment of the VOI. PVC has the potential to substantially improve the accuracy of tracer uptake assessment, provided that robust and accurate VOI methods become available. Commonly used delineation methods may not be adequate for this purpose.

Dual time-point FDG PET/CT and FDG uptake and related enzymes in lymphadenopathies: preliminary results.

The purpose of this study was to determine the ability of dual time-point (DTP) PET/CT with (18)F-FDG to discriminate between malignant and benign lymphadenopathies. The relationship between DTP FDG uptake and glucose metabolism/hypoxia markers in lymphadenopathies was also assessed. Patients with suspected lymphoma or recently diagnosed treatment-naive lymphoma were prospectively enrolled for DTP FDG PET/CT (scans 60min and 180min after FDG administration). FDG-avid nodal lesions were segmented to yield volume and standardized uptake values (SUV), including SUVmax, SUVmean, cSUVmean (with partial volume correction), total lesion glycolysis (TLG) and cTLG (with partial volume correction). Expression of glucose transporter-1 (GLUT-1), hexokinase-II (HK-II), glucose-6-phosphatase (G6Pase) and hypoxia-inducible factor-1alpha (HIF-1alpha) were assessed with immunohistochemistry and enzyme activity was determined for HK and G6Pase. FDG uptake was assessed in 203 lesions (146 malignant and 57 benign). Besides volume, there were significant increases over time for all parameters, with generally higher levels in the malignant lesions. The retention index (RI) was not able to discriminate between malignant and benign lesions. Volume, SUVmax, TLG and cTLG for both scans were able to discriminate between the two groups statistically, but without complete separation. Glucose metabolism/hypoxia markers were assessed in 15 lesions. TLG and cTLG were correlated with GLUT-1 expression on the 60-min scan. RI-max and RI-mean and SUVmax, SUVmean and cSUVmean on the 60-min scan were significantly correlated with HK-II expression. RI was not able to discriminate between malignant and benign lesions, but some of the SUVs were able to discriminate on the 60-min and 180-min scans. Furthermore, FDG uptake was correlated with GLUT-1 and HK-II expression.

Quantitative Amyloid Imaging in Autosomal Dominant Alzheimer's Disease: Results from the DIAN Study Group.

Amyloid imaging plays an important role in the research and diagnosis of dementing disorders. Substantial variation in quantitative methods to measure brain amyloid burden exists in the field. The aim of this work is to investigate the impact of methodological variations to the quantification of amyloid burden using data from the Dominantly Inherited Alzheimer’s Network (DIAN), an autosomal dominant Alzheimer’s disease population. Cross-sectional and longitudinal [11C]-Pittsburgh Compound B (PiB) PET imaging data from the DIAN study were analyzed. Four candidate reference regions were investigated for estimation of brain amyloid burden. A regional spread function based technique was also investigated for the correction of partial volume effects. Cerebellar cortex, brain-stem, and white matter regions all had stable tracer retention during the course of disease. Partial volume correction consistently improves sensitivity to group differences and longitudinal changes over time. White matter referencing improved statistical power in the detecting longitudinal changes in relative tracer retention; however, the reason for this improvement is unclear and requires further investigation. Full dynamic acquisition and kinetic modeling improved statistical power although it may add cost and time. Several technical variations to amyloid burden quantification were examined in this study. Partial volume correction emerged as the strategy that most consistently improved statistical power for the detection of both longitudinal changes and across-group differences. For the autosomal dominant Alzheimer’s disease population with PiB imaging, utilizing brainstem as a reference region with partial volume correction may be optimal for current interventional trials. Further investigation of technical issues in quantitative amyloid imaging in different study populations using different amyloid imaging tracers is warranted.

In vivo imaging of neurodegeneration in dementia with Lewy bodies (DLB).

For almost two decades, O'Brien and colleagues have investigated virtually every facet of dementia with Lewy bodies (DLB), phenomenology, treatment, and neurobiology, ranging from genetics to post-mortem and in vivo imaging studies. The latest study from this group, reported here, describes differences in regional grey matter volumes using magnetic resonance (MR) imaging and an automated segmentation analysis method in a well-characterized sample of patients with Alzheimer disease (AD), DLB, and a healthy control group (Watson et al., 2015). The study incorporated detailed psychometric assessments of cognitive and motor functions for correlation with the grey matter volumes, and age, gender and dementia severity were included as covariates in the statistical analysis. The key observations are relatively greater hippocampal volumes and lower subcortical volumes in DLB compared to AD, but it is to be noted that most of these differences in subcortical volume were demonstrated indirectly through comparisons of the disease groups with age-matched healthy control subjects. Thus, replication in studies that make direct comparisons between DLB and AD subjects, perhaps in a larger sample size, is necessary. Still, these results highlight the potential for MR imaging to provide indicators of the extent of the neurodegenerative process in DLB. Furthermore, the results underscore the importance of correcting molecular imaging data for the effects of cerebral atrophy (partial volume correction) that may further enhance the ability of these methods to reveal pathophysiological processes.

Patient motion effects on the quantification of regional myocardial blood flow with dynamic PET imaging.

Patient motion is a common problem during dynamic positron emission tomography (PET) scans for quantification of myocardial blood flow (MBF). The purpose of this study was to quantify the prevalence of body motion in a clinical setting and evaluate with realistic phantoms the effects of motion on blood flow quantification, including CT attenuation correction (CTAC) artifacts that result from PET-CT misalignment. A cohort of 236 sequential patients was analyzed for patient motion under resting and peak stress conditions by two independent observers. The presence of motion, affected time-frames, and direction of motion was recorded; discrepancy between observers was resolved by consensus review. Based on these results, patient body motion effects on MBF quantification were characterized using the digital NURBS-based cardiac-torso phantom, with characteristic time activity curves (TACs) assigned to the heart wall (myocardium) and blood regions. Simulated projection data were corrected for attenuation and reconstructed using filtered back-projection. All simulations were performed without noise added, and a single CT image was used for attenuation correction and aligned to the early- or late-frame PET images. In the patient cohort, mild motion of 0.5 ± 0.1 cm occurred in 24% and moderate motion of 1.0 ± 0.3 cm occurred in 38% of patients. Motion in the superior/inferior direction accounted for 45% of all detected motion, with 30% in the superior direction. Anterior/posterior motion was predominant (29%) in the posterior direction. Left/right motion occurred in 24% of cases, with similar proportions in the left and right directions. Computer simulation studies indicated that errors in MBF can approach 500% for scans with severe patient motion (up to 2 cm). The largest errors occurred when the heart wall was shifted left toward the adjacent lung region, resulting in a severe undercorrection for attenuation of the heart wall. Simulations also indicated that the magnitude of MBF errors resulting from motion in the superior/inferior and anterior/posterior directions was similar (up to 250%). Body motion effects were more detrimental for higher resolution PET imaging (2 vs 10 mm full-width at half-maximum), and for motion occurring during the mid-to-late time-frames. Motion correction of the reconstructed dynamic image series resulted in significant reduction in MBF errors, but did not account for the residual PET-CTAC misalignment artifacts. MBF bias was reduced further using global partial-volume correction, and using dynamic alignment of the PET projection data to the CT scan for accurate attenuation correction during image reconstruction. Patient body motion can produce MBF estimation errors up to 500%. To reduce these errors, new motion correction algorithms must be effective in identifying motion in the left/right direction, and in the mid-to-late time-frames, since these conditions produce the largest errors in MBF, particularly for high resolution PET imaging. Ideally, motion correction should be done before or during image reconstruction to eliminate PET-CTAC misalignment artifacts.

High resolution bone material property assignment yields robust subject specific finite element models of complex thin bone structures

Accurate finite element (FE) modeling of complex skeletal anatomy requires high resolution in both meshing and the heterogeneous mapping of material properties onto the generated mesh. This study introduces Node-based elastic Modulus Assignment with Partial-volume correction (NMAP) as a new approach for FE material property assignment to thin bone structures. The NMAP approach incorporates point spread function based deblurring of CT images, partial-volume correction of CT image voxel intensities and anisotropic interpolation and mapping of CT intensity assignment to FE mesh nodes. The NMAP procedure combined with a derived craniomaxillo-facial skeleton (CMFS) specific density-isotropic elastic modulus relationship was applied to produce specimen-specific FE models of 6 cadaveric heads. The NMAP procedure successfully generated models of the complex thin bone structures with surface elastic moduli reflective of cortical bone material properties. The specimen-specific CMFS FE models were able to accurately predict experimental strains measured under in vitro temporalis and masseter muscle loading (r=0.93, slope=1.01, n=5). The strength of this correlation represents a robust validation for CMFS FE modeling that can be used to better understand load transfer in this complex musculoskeletal system. The developed methodology offers a systematic process-flow able to address the complexity of the CMFS that can be further applied to create high-fidelity models of any musculoskeletal anatomy.

Different partial volume correction methods lead to different conclusions: An 18F-FDG-PET study of aging

A cross-sectional group study of the effects of aging on brain metabolism as measured with 18F-FDG-PET was performed using several different partial volume correction (PVC) methods: no correction (NoPVC), Meltzer (MZ), Müller-Gärtner (MG), and the symmetric geometric transfer matrix (SGTM) using 99 subjects aged 65–87years from the Harvard Aging Brain study. Sensitivity to parameter selection was tested for MZ and MG. The various methods and parameter settings resulted in an extremely wide range of conclusions as to the effects of age on metabolism, from almost no changes to virtually all of cortical regions showing a decrease with age. Simulations showed that NoPVC had significant bias that made the age effect on metabolism appear to be much larger and more significant than it is. MZ was found to be the same as NoPVC for liberal brain masks; for conservative brain masks, MZ showed few areas correlated with age. MG and SGTM were found to be similar; however, MG was sensitive to a thresholding parameter that can result in data loss. CSF uptake was surprisingly high at about 15% of that in gray matter. The exclusion of CSF from SGTM and MG models, which is almost universally done, caused a substantial loss in the power to detect age-related changes. This diversity of results reflects the literature on the metabolism of aging and suggests that extreme care should be taken when applying PVC or interpreting results that have been corrected for partial volume effects. Using the SGTM, significant age-related changes of about 7% per decade were found in frontal and cingulate cortices as well as primary visual and insular cortices.

Solvation Structure and Quasidynamics of Biomolecules Steered with Effective Solvation Forces Obtained From Molecular Theory of Solvation

Three-dimensional reference interaction site model with Kovalenko-Hirata closure (3D-RISM-KH molecular theory of solvation) is Ornstein-Zernike type integral equation theory of liquids. Based on first principles of statistical mechanics, 3D-RISM-KH consistently accounts for effect of chemical specificities of solvent, co-solvent, ions, and ligands on biomolecules solvation structure and thermodynamics, including steric forces, hydrophobicity, hydrogen bonding, and other effective interactions. 3D-RISM-KH supplemented with the partial molar volume correction, a.k.a. “Universal Correction” (UC), provides an excellent agreement with experimental data on a large set of small compounds for solvation free energies in octanol and water, and octanol-water partition coefficients. 3D-RISM-KH structural water detection and placement are implemented in Amber Tools and Molecular Operating Environment (MOE) packages. Structural water plays critical role in protein interactions and functions; case studies include HET-s prion, Aβ oligomer and fibril formation, folding promotion in GroEL chaperonin, and ligand binding to maltose-binding protein. Multi-time-step MD of biomolecules steered with mean solvation forces obtained from 3D-RISM-KH at outer steps and treated with generalized solvation force extrapolation (GSFE) at inner steps is efficiently stabilized with the optimized isokinetic Nose-Hoover chain (OIN) thermostat. The accuracy of GSFE and efficiency of OIN allow picoseconds outer steps while accurately reproducing conformational properties, as validated on hydrated alanine dipeptide, miniprotein 1L2Y, and protein G. Due to 3D-RISM-KH statistical averaging over rare events of solvent exchange and localization in biomolecular spaces, this quasidynamics results in time scale compression of protein conformational changes coupled with solvent and so in huge acceleration of conformational sampling. This provides up to 1000-fold effective speedup of sampling, compared to conventional MD with explicit solvent, and enables to fold the miniprotein from a fully denatured state in 60ns quasidynamics, cf. 4-9μs folding time in experiment.

Impact of CT-based Attenuation Correction on the Registration Between Dual-gated Cardiac PET and High-Resolution CT

A high-resolution CT (HRCT) used as anatomical prior information during PET reconstruction can enhance the quality of a corresponding low-resolution PET image, provided that it is accurately registered to the PET dataset of interest. In this work, the impact of different PET/CT attenuation correction (AC) protocols on the registration between a dual-gated cardiac $^{18}{\rm F}$ -FDG PET image and an HRCT image is investigated. The aim is to explore the impact of AC on PET-to-HRCT registration, and to identify the AC strategy that yields the best alignment between the left-ventricles in the PET and the HRCT images for subsequent partial volume correction. Simulations were performed using XCAT phantoms. Shallow breathing and a regular beating pattern were simulated and both noise-free and noisy data were evaluated. Respiratory motion during the acquisition of the CT used for attenuation correction strongly affected the dual-gated PET reconstructions, resulting in artefacts and quantification errors in the PET image and poor PET-to-HRCT registration accuracy. The blurring introduced by the beating heart, on the other hand, proved to have a negligible effect on PET-CT registration. Dual-gated PET images reconstructed without attenuation correction could be well registered to the HRCT if a good initial alignment between the starting images was provided. A commercially available strategy to deal with an AC CT that is acquired in the wrong respiratory phase was also evaluated, and yielded not only enhanced quantitative accuracy but also accurate PET-to-HRCT registration. The effect of a high level of noise, as present in a dual-gated cardiac PET study, was also investigated. Registrations proved to be sensitive to noise, but noise is not a major limiting factor for PET-to-HRCT registration. A selection of the investigated attenuation correction procedures was also evaluated using cardiac PET/CT data measured in sheep. The PET-to-HRCT registration performance confirmed the XCAT-based predictions.

Eliminating the blood-flow confounding effect in intravoxel incoherent motion (IVIM) using the non-negative least square analysis in liver.

Tissue perfusion measurements using intravoxel incoherent motion (IVIM) diffusion-MRI are of interest for investigations of liver pathologies. A confounding factor in the perfusion quantification is the partial volume between liver tissue and large blood vessels. The aim of this study was to assess and correct for this partial volume effect in the estimation of the perfusion fraction. MRI experiments were performed at 3 Tesla with a diffusion-MRI sequence at 12 b-values. Diffusion signal decays in liver were analyzed using the non-negative least square (NNLS) method and the biexponential fitting approach. In some voxels, the NNLS analysis yielded a very fast-decaying component that was assigned to partial volume with the blood flowing in large vessels. Partial volume correction was performed by biexponential curve fitting, where the first data point (b = 0 s/mm2 ) was eliminated in voxels with a very fast-decaying component. Biexponential fitting with partial volume correction yielded parametric maps with perfusion fraction values smaller than biexponential fitting without partial volume correction. The results of the current study indicate that the NNLS analysis in combination with biexponential curve fitting allows to correct for partial volume effects originating from blood flow in IVIM perfusion fraction measurements. Magn Reson Med 77:310-317, 2017. © 2016 Wiley Periodicals, Inc.

Hitchhiker's Guide to Voxel Segmentation for Partial Volume Correction of In Vivo Magnetic Resonance Spectroscopy.

Partial volume effects have the potential to cause inaccuracies when quantifying metabolites using proton magnetic resonance spectroscopy (MRS). In order to correct for cerebrospinal fluid content, a spectroscopic voxel needs to be segmented according to different tissue contents. This article aims to detail how automated partial volume segmentation can be undertaken and provides a software framework for researchers to develop their own tools. While many studies have detailed the impact of partial volume correction on proton magnetic resonance spectroscopy quantification, there is a paucity of literature explaining how voxel segmentation can be achieved using freely available neuroimaging packages.

Quantitatively accurate activity measurements with a dedicated cardiac SPECT camera: Physical phantom experiments.

Recently, there has been increased interest in dedicated cardiac single photon emission computed tomography (SPECT) scanners with pinhole collimation and improved detector technology due to their improved count sensitivity and resolution over traditional parallel-hole cameras. With traditional cameras, energy-based approaches are often used in the clinic for scatter compensation because they are fast and easily implemented. Some of the cardiac cameras use cadmium-zinc-telluride (CZT) detectors which can complicate the use of energy-based scatter correction (SC) due to the low-energy tail-an increased number of unscattered photons detected with reduced energy. Modified energy-based scatter correction methods can be implemented, but their level of accuracy is unclear. In this study, the authors validated by physical phantom experiments the quantitative accuracy and reproducibility of easily implemented correction techniques applied to (99m)Tc myocardial imaging with a CZT-detector-based gamma camera with multiple heads, each with a single-pinhole collimator. Activity in the cardiac compartment of an Anthropomorphic Torso phantom (Data Spectrum Corporation) was measured through 15 (99m)Tc-SPECT acquisitions. The ratio of activity concentrations in organ compartments resembled a clinical (99m)Tc-sestamibi scan and was kept consistent across all experiments (1.2:1 heart to liver and 1.5:1 heart to lung). Two background activity levels were considered: no activity (cold) and an activity concentration 1/10th of the heart (hot). A plastic "lesion" was placed inside of the septal wall of the myocardial insert to simulate the presence of a region without tracer uptake and contrast in this lesion was calculated for all images. The true net activity in each compartment was measured with a dose calibrator (CRC-25R, Capintec, Inc.). A 10 min SPECT image was acquired using a dedicated cardiac camera with CZT detectors (Discovery NM530c, GE Healthcare), followed by a CT scan for attenuation correction (AC). For each experiment, separate images were created including reconstruction with no corrections (NC), with AC, with attenuation and dual-energy window (DEW) scatter correction (ACSC), with attenuation and partial volume correction (PVC) applied (ACPVC), and with attenuation, scatter, and PVC applied (ACSCPVC). The DEW SC method used was modified to account for the presence of the low-energy tail. T-tests showed that the mean error in absolute activity measurement was reduced significantly for AC and ACSC compared to NC for both (hot and cold) datasets (p < 0.001) and that ACSC, ACPVC, and ACSCPVC show significant reductions in mean differences compared to AC (p ≤ 0.001) without increasing the uncertainty (p > 0.4). The effect of SC and PVC was significant in reducing errors over AC in both datasets (p < 0.001 and p < 0.01, respectively), resulting in a mean error of 5% ± 4%. Quantitative measurements of cardiac (99m)Tc activity are achievable using attenuation and scatter corrections, with the authors' dedicated cardiac SPECT camera. Partial volume corrections offer improvements in measurement accuracy in AC images and ACSC images with elevated background activity; however, these improvements are not significant in ACSC images with low background activity.