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1.
Appl Opt ; 58(13): D98-D104, 2019 May 01.
Article in English | MEDLINE | ID: mdl-31044871

ABSTRACT

The Florida Everglades is infested with Burmese pythons caused by the release of exotic pets in the 1980s. The current estimates are between 30,000 and 300,000 pythons, where the result is a severe decline in Everglade mammals: 90% reductions in raccoon, opossum, bobcats, and foxes. The marsh rabbits are completely gone. The population of the pythons is rapidly increasing exponentially with 20-50 eggs per snake with a life span of up to 20 years. Pythons have been captured in the Everglades with lengths of nearly 6 m. Researchers in the state of Florida are concerned that these pythons are (1) permanently damaging the Everglades, (2) migrating further north into populated areas of Florida, and (3) endangering wildlife, pets, and eventually, people. There have been a number of sensing efforts attempted in the large-area detection of pythons, where limited success has been achieved. For example, infrared sensors have been applied to the problem, but the pythons are cold-blooded, so the infrared bands do not work well. Imec has leveraged its expertise and infrastructure in semiconductor processing to produce highly compact, higher performance, and relatively cheaper hyperspectral image sensors and camera systems. In this work, Imec teamed with the University of Florida and Extended Reality Systems to obtain hyperspectral reflectivity measurements of Burmese pythons along with natural Florida background foliage to determine bands or band combinations that may be exploited in the large-area detection of pythons. The bands investigated are the visible-near infrared (or VisNIR) and the shortwave infrared (SWIR) bands. The results show that there are enough differences in the data collection such that a single band, inexpensive VisNIR band camera may provide reasonable results and a two-band, VisNIR/SWIR combination may provide higher performance results. In this paper, we provide the VisNIR results.


Subject(s)
Boidae/physiology , Ecosystem , Photography/instrumentation , Skin Physiological Phenomena , Whole Body Imaging/methods , Animals , Environment , Florida , Optics and Photonics
2.
J Cardiovasc Pharmacol ; 62(3): 304-11, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23714775

ABSTRACT

Identification of myocardial infarction (MI) by imaging is critical for clinical management of ischemic heart disease. Iodine-123-labeled hypericin (¹²³I-Hyp) is a new potent infarct avid agent. We sought to compare target selectivity and organ distribution between ¹²³I-Hyp and the myocardial perfusion agent, technetium-99m-labeled hexakis [2-methoxy isobutyl isonitrile] ((99m)Tc-Sestamibi) in rabbits with acute MI. Hypericin was radiolabeled with I using iodogen as oxidant, and (99m)Tc-Sestamibi was prepared from a commercial kit and radioactive sodium pertechnetate. Rabbits (n = 6) with 24-hour-old MI received ¹²³I-Hyp intravenously and received (99m)Tc-Sestamibi 9 hours later. They were studied by dual-isotope simultaneous acquisition micro single photon emission computed tomography/computed tomography (DISA-µSPECT/CT), tissue gamma counting (TGC), autoradiography, and histology. After purification, ¹²³I-Hyp was obtained with radiochemical purity around 99%. DISA-µSPECT/CT images showed ¹²³I-Hyp retention in infarcted but not in normal myocardium. By TGC, accumulation values reached 1.175 ± 0.096 percentage of injected dose per gram (%ID/g) and 0.028 ± 0.007%ID/g in infarcted myocardium and normal myocardium with high tracer concentration in liver, intestines, and gallbladder. (99m)Tc-Sestamibi was prepared with radiochemical purity over 95%. DISA-µSPECT/CT showed no accumulation in MI and high initial radioactivity levels in normal myocardium that were rapidly cleared as confirmed by TGC (0.011 ± 0.003%ID/g). Liver and intestines were clearly visualized. By TGC, gallbladder and kidneys show moderate (99m)Tc-Sestamibi uptake. The selectivity of ¹²³I-Hyp for infarcted myocardium and (99m)Tc-Sestamibi for normal myocardium was confirmed. ¹²³I-Hyp distribution in rabbits is characterized by hepatobiliary excretion. (99m)Tc-Sestamibi undergoes hepatorenal elimination.


Subject(s)
Coronary Vessels/diagnostic imaging , Disease Models, Animal , Heart/diagnostic imaging , Myocardial Infarction/diagnostic imaging , Perylene/analogs & derivatives , Radiopharmaceuticals , Technetium Tc 99m Sestamibi/pharmacokinetics , Animals , Anthracenes , Autoradiography , Coronary Circulation , Coronary Vessels/pathology , Gamma Cameras , Half-Life , Iodine Radioisotopes , Male , Myocardial Infarction/pathology , Myocardium/pathology , Necrosis , Perylene/pharmacokinetics , Rabbits , Radionuclide Imaging , Technetium , Tissue Distribution , Tomography, X-Ray Computed
3.
Bioorg Med Chem Lett ; 21(1): 502-5, 2011 Jan 01.
Article in English | MEDLINE | ID: mdl-21075631

ABSTRACT

N,N'-bis(diethylenetriamine pentaacetic acid)-3,3'-(benzylidene)-bis-(1H-indole-2-carbohydrazide) (bis-DTPA-BI) was radiolabeled with (99m)Tc(CO)(3). The resulting (99m)Tc(CO)(3)-bis-DTPA-BI was characterized (LC-MS) and evaluated as a potential SPECT tracer for imaging of necrosis in Wistar rats with a reperfused partial liver infarction and Wistar rats with ethanol induced muscular necrosis. To study the specificity, uptake of (99m)Tc(CO)(3)-bis-DTPA-BI was also studied in a mouse model of Fas-mediated hepatic apoptosis. The obtained results indicate that (99m)Tc(CO)(3)-bis-DTPA-BI displays selective uptake in necrotic tissue and can be used for in vivo visualization of necrosis by SPECT.


Subject(s)
Indoles/chemistry , Necrosis/diagnosis , Organotechnetium Compounds/chemistry , Pentetic Acid/analogs & derivatives , Radiopharmaceuticals/chemistry , Animals , Apoptosis , Hepatocytes/pathology , Indoles/chemical synthesis , Isotope Labeling , Mice , Pentetic Acid/chemical synthesis , Pentetic Acid/chemistry , Radiopharmaceuticals/chemical synthesis , Rats , Rats, Wistar , Tissue Distribution , Tomography, Emission-Computed, Single-Photon
4.
Bioorg Med Chem ; 18(3): 1356-63, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20053567

ABSTRACT

In this study 'second generation' AnxV was specifically labeled with (99m)Tc in three different ways outside the binding region of the protein to obtain an improved target-to-background activity ratio. The compounds were tested in vitro and in vivo in normal mice and in a model of hepatic apoptosis (anti-Fas mAb). The apoptosis binding was most prominent for the HIS-tagged 'second generation' AnxV labeled with (99m)Tc(CO)(3) in comparison to (99m)Tc-HYNIC-cys-AnxV and (99m)Tc(CO)(3)-DTPA-cys-AnxV.


Subject(s)
Annexin A5 , Apoptosis , Technetium , Tomography, Emission-Computed, Single-Photon/methods , Animals , Annexin A5/chemistry , Hepatocytes/cytology , Mice , Technetium/chemistry
5.
Methods ; 48(2): 83-91, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19328232

ABSTRACT

With Single Photon Emission Computed Tomography (SPECT), images of minute concentrations of tracer molecules can be acquired, allowing in vivo molecular imaging. For human imaging, the SPECT system has a modest spatial resolution of 5-15 mm, a large field of view and a high sensitivity. Using multi-pinhole SPECT, one can trade in field of view for resolution with preserved sensitivity, which enables the implementation of a small animal SPECT system with an improved resolution, currently ranging from 0.3 to 2 mm, in a much smaller field of view. The unconventional collimation and the more stringent resolution requirements pose problems that are not present in clinical SPECT imaging. This paper discusses how these problems can be solved to implement micro-SPECT imaging on a rotating gamma camera.


Subject(s)
Molecular Diagnostic Techniques/methods , Tomography, Emission-Computed, Single-Photon/methods , Animals , Artifacts , Calibration , Gamma Cameras , Phantoms, Imaging , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon/instrumentation
6.
Cardiol J ; 26(4): 375-384, 2019.
Article in English | MEDLINE | ID: mdl-29570208

ABSTRACT

BACKGROUND: Pacing the right heart has been shown to induce reversible conduction delay and subse-quent asymmetric remodeling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments. Therefore the aim of this study was to develop a more feasible and easy-to-use animal model in sheep. METHODS: Dual-chamber (DDD) pacemakers with epicardial leads on the right atrium and right ven-tricular free wall were implanted in 13 sheep. All animals underwent 8 weeks of chronic rapid pacing at 180 bpm. Reported observations were made at 110 bpm. RESULTS: DDD pacing acutely induced a left bundle branch block (LBBB) - like pattern with almost doubling in QRS width and the appearance of a septal flash, indicating mechanical dyssynchrony. Atrial pacing (AAI) resulted in normal ventricular conduction and function. During 8 weeks of rapid DDD pacing, animals developed LV remodeling (confirmed with histology) with septal wall thinning (-30%, p < 0.05), lateral wall thickening (+22%, p < 0.05), LV volume increase (+32%, p < 0.05), decrease of LV ejection fraction (-31%, p < 0.05), and functional mitral regurgitation. After 8 weeks, segmental pressure-strain-loops, representing regional myocardial work, were recorded. Switching from AAI to DDD pacing decreased immediately work in the septum and increased it in the lateral wall (-69 and +41%, respectively, p < 0.05). Global LV stroke work and dP/dtmax decreased (-27% and -25%, respectively, p < 0.05). CONCLUSIONS: This study presents the development a new sheep model with an asymmetrically remod-eled LV. Simple pacemaker programing allows direct modulation of regional myocardial function and work. This animal model provides a new and valuable alternative for canine or porcine models and has the potential to become instrumental for investigating regional function and loading conditions on regional LV remodeling.


Subject(s)
Bundle-Branch Block/physiopathology , Cardiac Pacing, Artificial , Heart Conduction System/physiopathology , Heart Rate , Hypertrophy, Left Ventricular/physiopathology , Ventricular Dysfunction, Left/physiopathology , Ventricular Function, Left , Ventricular Remodeling , Action Potentials , Animals , Bundle-Branch Block/diagnosis , Bundle-Branch Block/etiology , Disease Models, Animal , Disease Progression , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/etiology , Male , Mitral Valve Insufficiency/etiology , Mitral Valve Insufficiency/physiopathology , Sheep, Domestic , Stroke Volume , Time Factors , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology , Ventricular Pressure
7.
Eur Heart J Cardiovasc Imaging ; 20(1): 84-91, 2019 01 01.
Article in English | MEDLINE | ID: mdl-29584821

ABSTRACT

Aims: Left ventricular (LV) dilatation results in increased sphericity and affects position and orientation of papillary muscles (PMs), which may influence their performed work. The aim of this study was to assess the contribution of PM to LV function and its changes with dilatation. Methods and results: Fifteen sheep were investigated. Ten animals were subjected to 8 weeks of rapid (180 bpm) pacing, inducing LV dilatation. Five animals served as controls. High-resolution gated computed tomography was performed to assess LV volumes, left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), sphericity index, and PM angle, width and fractional shortening. 18F-fluorodeoxyglucose positron emission tomography (PET) was used to measure glucose metabolism as surrogate of regional myocardial work. Spatial resolution of PET images was maximized by electrocardiogram- and respiratory-gating. 18F-fluorodeoxyglucose uptake was measured in PM and compared with remaining left ventricular myocardium (MYO) to obtain a PM/MYO ratio. Animals with dilated heart had a more spherical left ventricle, with reduced LVEF (P < 0.0001) and GLS (P < 0.0001). In dilated hearts, PET analysis revealed a higher contribution of both PM to LV myocardial work (P < 0.0001); and PM angle towards LV wall correlated with PM work, together with PM width and the LV sphericity index. Sphericity index and posterior PM angle were strongest determinants of posterior PM/MYO ratio (R2 = 0.754; P < 0.0001), while anterior PM/MYO was mostly determined by sphericity index and the PM width (R2 = 0.805; P < 0.0001). Conclusion: In dilated hearts, PM contribute relatively more to LV myocardial work. We hypothesize that this is caused by the more cross-sectional orientation of the subvalvular apparatus, which leads to a higher stress on the PM compared with the spherical LV walls. The reduced cross-sectional area of the PM may further explain their increased stress.


Subject(s)
Papillary Muscles/diagnostic imaging , Papillary Muscles/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology , Animals , Cardiac-Gated Imaging Techniques , Disease Models, Animal , Female , Fluorodeoxyglucose F18 , Heart Rate/physiology , Positron-Emission Tomography , Proof of Concept Study , Radiopharmaceuticals , Respiratory-Gated Imaging Techniques , Sheep , Sheep, Domestic , Stroke Volume , Tomography, X-Ray Computed
8.
Circ Arrhythm Electrophysiol ; 12(5): e007224, 2019 05.
Article in English | MEDLINE | ID: mdl-31023060

ABSTRACT

BACKGROUND: The interaction between regional left ventricular (LV) myocardial work and metabolism in remodeled hearts has not yet been well established. Our aim was to investigate the effect of inhomogeneous LV work distribution on regional metabolism and remodeling in our animal model with reversible dyssynchrony due to pacing. METHODS: In 12 sheep, 8 weeks of right atrial and right ventricular free wall (DDD) pacing lead to LV dilatation, a thinned septum, and thickened lateral wall. Left bundle branch block-like dyssynchrony caused by DDD pacing could be acutely reverted by right atrial pacing (AAI) only. Invasive hemodynamics and echocardiography were used to assess regional work by stress-strain loop area and compared with regional glucose metabolism measured by 18F-fluorodeoxyglucose positron emission tomography with and without improved spatial resolution by motion and anatomy correction on gated reconstructions. RESULTS: Glucose metabolism by positron emission tomography with anatomic correction on gated positron emission tomography reconstruction showed a different regional distribution than with clinical reconstructions and correlated best and significantly with regional myocardial work. At baseline, work was homogeneously distributed with normal conduction (AAI pacing), whereas during dyssynchrony (DDD pacing), the lateral wall was more loaded, and the septum was unloaded. After 8 weeks of remodeling under DDD pacing, however, an almost homogeneous work distribution was found with DDD pacing, whereas with AAI pacing, the thin septum showed exaggerated loading and the lateral walls a low load. Our experimental observations were confirmed in 5 patient responders to cardiac resynchronization therapy. CONCLUSIONS: Regional LV glucose metabolism closely correlates with regional work. Our data indicate that regionally different LV remodeling after exposure to inhomogeneous loading conditions, such as during LV dyssynchrony, is an adaptive process that helps to equilibrate work distribution. Correction of the inhomogeneous loading conditions, such as during cardiac resynchronization therapy, then triggers a reverse LV remodeling through the same mechanism.


Subject(s)
Energy Metabolism , Hypertrophy, Left Ventricular/physiopathology , Myocardium/metabolism , Ventricular Dysfunction, Left/physiopathology , Ventricular Function, Left , Ventricular Remodeling , Adaptation, Physiological , Animals , Cardiac Pacing, Artificial , Disease Models, Animal , Female , Fluorodeoxyglucose F18/administration & dosage , Glucose/metabolism , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/metabolism , Positron-Emission Tomography , Radiopharmaceuticals/administration & dosage , Sheep, Domestic , Time Factors , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/metabolism
9.
Bioorg Med Chem Lett ; 18(13): 3794-8, 2008 Jul 01.
Article in English | MEDLINE | ID: mdl-18524580

ABSTRACT

A novel cys-annexin A5 with a single cysteine-residue at its concave side has been developed by site-directed mutagenesis to allow conjugation through thiol-chemistry without affecting its apoptotic cell binding properties and was derivatized with HYNIC in a 1:1 stoichiometry. Similar to that of the 1st generation 99mTc-HYNIC-annexin A5, the novel 99mTc-HYNIC-cys-annexin A5 derivative shows in normal mice mainly renal and, to a lesser extent, hepatobiliary excretion. In murine models of hepatic apoptosis there was 257% increase in hepatic uptake of 99mTc-HYNIC-cys-annexin A5 as compared to normal mice. Using the novel tracer agent, acute reperfused myocardial infarction in rabbits was unequivocally delineated at 7h post-injection by muSPECT. The results indicate that the novel 99mTc-HYNIC-cys-annexin A5 shows similar apoptosis avidity as the 1st generation 99mTc-HYNIC-annexin A5.


Subject(s)
Annexin A5/chemistry , Apoptosis , Cysteine/analogs & derivatives , Organotechnetium Compounds/pharmacology , Animals , Annexin A5/pharmacology , Chemistry, Pharmaceutical/methods , Cysteine/chemistry , Cysteine/pharmacology , Drug Design , Liver/metabolism , Mice , Models, Chemical , Myocardial Infarction/metabolism , Rabbits , Sulfhydryl Compounds/chemistry , Tomography, Emission-Computed, Single-Photon/methods
10.
IEEE Trans Med Imaging ; 37(2): 590-603, 2018 02.
Article in English | MEDLINE | ID: mdl-29408787

ABSTRACT

In this article, we evaluate Parallel Level Sets (PLS) and Bowsher's method as segmentation-free anatomical priors for regularized brain positron emission tomography (PET) reconstruction. We derive the proximity operators for two PLS priors and use the EM-TV algorithm in combination with the first order primal-dual algorithm by Chambolle and Pock to solve the non-smooth optimization problem for PET reconstruction with PLS regularization. In addition, we compare the performance of two PLS versions against the symmetric and asymmetric Bowsher priors with quadratic and relative difference penalty function. For this aim, we first evaluate reconstructions of 30 noise realizations of simulated PET data derived from a real hybrid positron emission tomography/magnetic resonance imaging (PET/MR) acquisition in terms of regional bias and noise. Second, we evaluate reconstructions of a real brain PET/MR data set acquired on a GE Signa time-of-flight PET/MR in a similar way. The reconstructions of simulated and real 3D PET/MR data show that all priors were superior to post-smoothed maximum likelihood expectation maximization with ordered subsets (OSEM) in terms of bias-noise characteristics in different regions of interest where the PET uptake follows anatomical boundaries. Our implementation of the asymmetric Bowsher prior showed slightly superior performance compared with the two versions of PLS and the symmetric Bowsher prior. At very high regularization weights, all investigated anatomical priors suffer from the transfer of non-shared gradients.


Subject(s)
Brain/diagnostic imaging , Image Processing, Computer-Assisted/methods , Positron-Emission Tomography/methods , Algorithms , Humans , Magnetic Resonance Imaging , Phantoms, Imaging
11.
Nucl Med Biol ; 34(3): 283-91, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17383578

ABSTRACT

INTRODUCTION: Cytosolic thymidine kinase (TK1) catalyzes phosphorylation of thymidine to its monophosphate. TK1 activity is closely related with DNA synthesis, and thymidine analogs derivatized with bulky carboranylalkyl groups at the N-3 position were reported to be good substrates for TK1. Accordingly, we have synthesized (99m)Tc-MAMA-propyl-thymidine and evaluated it as a potential tumor tracer. METHODS: The bis(S-trityl)-protected MAMA-propyl-thymidine precursor (3-N-[S-trityl-2-mercaptoethyl]-N-[N'-(S-trityl-2-mercaptoethyl)amidoacetyl]-aminopropyl-thymidine) was prepared in three steps, and its structure was confirmed with (1)H NMR and mass spectrometry. Deprotection of the thiols and labeling with (99m)Tc were done in a two-step, one-pot procedure, yielding (99m)Tc-MAMA-propyl-thymidine, which was analyzed with high-performance liquid chromatography, radio-LC-MS analysis (ESI+) and electrophoresis, and its log P was determined. The biodistribution in normal mice was evaluated, and its biodistribution in a radiation-induced fibrosarcoma (RIF) tumor mouse was compared with that of 3'-deoxy-3'-[(18)F] fluorothymidine [(18)F]FLT. RESULTS: (99m)Tc-MAMA-propyl-thymidine was obtained with a radiochemical yield of 70%. Electrophoresis indicated that the complex is uncharged, and its log P was 1.0. The molecular ion mass of the Tc complex was 589 Da, which is compatible with the hypothesized N(2)S(2)-oxotechnetium structure. Tissue distribution showed fast clearance from plasma primarily by the hepatobiliary pathway. Whole-body planar imaging after injection of (99m)Tc-MAMA-propyl-thymidine in an RIF tumor-bearing mouse showed high uptake in the liver and the intestines. No uptake was observed in the tumor, in contrast to the clear uptake observed for [(18)F] FLT visualized with muPET. CONCLUSIONS: Although it has been reported that TK1 accepts large substituents at the N-3 position of the thymine ring, the results of this study show that (99m)Tc-MAMA-propyl-thymidine cannot be used as a single photon emission computed tomography tumor tracer, probably because the (99m)Tc-MAMA ligand is too bulky to be tolerated by TK1.


Subject(s)
Fibrosarcoma/diagnostic imaging , Fibrosarcoma/metabolism , Organotechnetium Compounds/pharmacokinetics , Tomography, Emission-Computed, Single-Photon/methods , Animals , Cell Proliferation , Drug Evaluation, Preclinical/methods , Feasibility Studies , Metabolic Clearance Rate , Mice , Mice, Nude , Molecular Probe Techniques , Neoplasm Staging , Organ Specificity , Organotechnetium Compounds/chemistry , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Tissue Distribution
12.
EJNMMI Phys ; 3(1): 9, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27316644

ABSTRACT

BACKGROUND: The 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 (18)F-FDG PET. METHODS: Simulated datasets, obtained with the XCAT software, are reconstructed with different algorithms and are quantitatively analysed. RESULTS: The 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. CONCLUSIONS: The 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.

13.
Neurobiol Aging ; 35(12): 2858-2869, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25018107

ABSTRACT

Several lines of evidence imply early alterations in endocannabinoid and phosphodiesterase 10A (PDE10A) signaling in Huntington disease (HD). Using [(18)F]MK-9470 and [(18)F]JNJ42259152 small-animal positron emission tomography (PET), we investigated for the first time cerebral changes in type 1 cannabinoid (CB1) receptor binding and PDE10A levels in vivo in presymptomatic, early symptomatic, and late symptomatic HD (R6/2) mice, in relation to glucose metabolism ([(18)F]FDG PET), brain morphology (magnetic resonance imaging) and motor function. Ten R6/2 and 16 wild-type (WT) mice were investigated at 3 different time points between the age of 4 and 13 weeks. Parametric CB1 receptor and PDE10A images were anatomically standardized to Paxinos space and analyzed voxelwise. Volumetric microMRI imaging was performed to assess HD pathology. In R6/2 mice, CB1 receptor binding was decreased in comparison with WT in a cluster comprising the bilateral caudate-putamen, globus pallidus, and thalamic nucleus at week 5 (-8.1% ± 2.6%, p = 1.7 × 10(-5)). Longitudinal follow-up showed further progressive decline compared with controls in a cluster comprising the bilateral hippocampus, caudate-putamen, globus pallidus, superior colliculus, thalamic nucleus, and cerebellum (late vs. presymptomatic age: -13.7% ± 3.1% for R6/2 and +1.5% ± 4.0% for WT, p = 1.9 × 10(-5)). In R6/2 mice, PDE10A binding potential also decreased over time to reach significance at early and late symptomatic HD (late vs. presymptomatic age: -79.1% ± 1.9% for R6/2 and +2.1% ± 2.7% for WT, p = 1.5 × 10(-4)). The observed changes in CB1 receptor and PDE10A binding were correlated to anomalies exhibited by R6/2 animals in motor function, whereas no correlation was found with magnetic resonance imaging-based striatal volume. Our findings point to early regional dysfunctions in endocannabinoid and PDE10A signaling, involving the caudate-putamen and lateral globus pallidus, which may play a role in the progression of the disease in R6/2 animals. PET quantification of in vivo CB1 and/or PDE10A binding may thus be useful early biomarkers for HD. Our results also provide evidence of subtle motor deficits at earlier stages than previously described.


Subject(s)
Brain/metabolism , Brain/pathology , Huntington Disease/genetics , Huntington Disease/pathology , Phosphoric Diester Hydrolases/genetics , Phosphoric Diester Hydrolases/metabolism , Receptor, Cannabinoid, CB1/genetics , Receptor, Cannabinoid, CB1/metabolism , Animals , Disease Progression , Female , Genetic Association Studies , Glucose/metabolism , Huntington Disease/metabolism , Magnetic Resonance Imaging , Male , Mice, Inbred C57BL , Mice, Transgenic , Protein Binding/genetics , Signal Transduction/genetics , Signal Transduction/physiology
14.
PLoS One ; 8(6): e65286, 2013.
Article in English | MEDLINE | ID: mdl-23762335

ABSTRACT

UNLABELLED: Automated voxel-based or pre-defined volume-of-interest (VOI) analysis of small-animal PET data in mice is necessary for optimal information usage as the number of available resolution elements is limited. We have mapped metabolic ([(18)F]FDG) and dopamine transporter ([(18)F]FECT) small-animal PET data onto a 3D Magnetic Resonance Microscopy (MRM) mouse brain template and aligned them in space to the Paxinos co-ordinate system. In this way, ligand-specific templates for sensitive analysis and accurate anatomical localization were created. Next, using a pre-defined VOI approach, test-retest and intersubject variability of various quantification methods were evaluated. Also, the feasibility of mouse brain statistical parametric mapping (SPM) was explored for [(18)F]FDG and [(18)F]FECT imaging of 6-hydroxydopamine-lesioned (6-OHDA) mice. METHODS: Twenty-three adult C57BL6 mice were scanned with [(18)F]FDG and [(18)F]FECT. Registrations and affine spatial normalizations were performed using SPM8. [(18)F]FDG data were quantified using (1) an image-derived-input function obtained from the liver (cMRglc), using (2) standardized uptake values (SUVglc) corrected for blood glucose levels and by (3) normalizing counts to the whole-brain uptake. Parametric [(18)F]FECT binding images were constructed by reference to the cerebellum. Registration accuracy was determined using random simulated misalignments and vectorial mismatch determination. RESULTS: Registration accuracy was between 0.21-1.11 mm. Regional intersubject variabilities of cMRglc ranged from 15.4% to 19.2%, while test-retest values were between 5.0% and 13.0%. For [(18)F]FECT uptake in the caudate-putamen, these values were 13.0% and 10.3%, respectively. Regional values of cMRglc positively correlated to SUVglc measured within the 45-60 min time frame (spearman r = 0.71). Next, SPM analysis of 6-OHDA-lesioned mice showed hypometabolism in the bilateral caudate-putamen and cerebellum, and an unilateral striatal decrease in DAT availability. CONCLUSION: MRM-based small-animal PET templates facilitate accurate assessment and spatial localization of mouse brain function using VOI or voxel-based analysis. Regional intersubject- and test-retest variations indicate that for these targets accuracy comparable to humans can be achieved.


Subject(s)
Anatomy, Artistic , Atlases as Topic , Brain Mapping , Cocaine/analogs & derivatives , Fluorodeoxyglucose F18 , Models, Statistical , Positron-Emission Tomography , Animals , Brain/diagnostic imaging , Brain/pathology , Cocaine/pharmacokinetics , Fluorodeoxyglucose F18/pharmacokinetics , Image Processing, Computer-Assisted , Male , Mice , Mice, Inbred C57BL , Oxidopamine
15.
Int J Cardiol ; 168(4): 4191-8, 2013 Oct 09.
Article in English | MEDLINE | ID: mdl-23932045

ABSTRACT

BACKGROUND: Necrosis avid tracer (123)I-hypericin ((123)I-HYP) enables hot-spot imaging on acute myocardial infarction (MI). We explored dual-isotope simultaneous acquisition single photon emission computed tomography/computed tomography (DISA-SPECT/CT) by using (123)I-HYP and standard (99m)Tc-sestamibi ((99m)Tc-MIBI), in comparison with cardiac magnetic resonance imaging (cMRI), autoradiography (AutoRx) and histomorphometry. METHODS: Acute MI was induced by 90-min coronary artery occlusion and 24-h reperfusion in 9 rabbits. They were scanned with cMRI at 3.0T, followed by intravenous injections of (123)I-HYP, and 8h later, of (99m)Tc-MIBI. Then, they were imaged with DISA-SPECT/CT for detection and localization of MI. The excised heart was sectioned for AutoRx, triphenyltetrazolium chloride (TTC) histochemistry, and haematoxylin-eosin (HE) staining. DISA-SPECT/CT and cMRI were co-registered, and MI was compared between different modalities and techniques for correlation with ex vivo findings. Tracer/contrast uptakes were quantified on polar maps. One way-ANOVA and Bonferroni's tests were used for comparison of multiple techniques. Linear regression and Bland-Altman analysis were used to compare measurements of MI. RESULTS: MI volumes were not significantly different as by (99m)Tc-MIBI-SPECT, (123)I-HYP-SPECT, cMRI and TTC (38.94 ± 13.97%, 37.76 ± 13.16%, 35.19 ± 12.53% and 33.26 ± 10.65%; p > 0.05). The MI areas were 41.13 ± 18.70%, 40.19 ± 18.45%, 38.23 ± 16.86%, 36.83 ± 16.70%, 36.16 ± 16.15% and 35.03 ± 14.75% on (99m)Tc-MIBI-SPECT, (123)I-HYP-SPECT, cMRI, AutoRx, TTC and HE. There was no significant differences between each of two techniques (p = 0.9). Tracer/contrast uptakes were well correlated ((123)I-HYP vs (99m)Tc-MIBI r(2) = 0.66; (123)I-HYP vs cMRI r(2) = 0.63; (99m)Tc-MIBI vs cMRI r(2) = 0.64). Infarct/normal myocardium activity ratio was 40/1 and 23/1 by AutoRx and γ-counting. CONCLUSION: (123)I-HYP has shown pronounced necrosis-avidity, which proves complementary for imaging MI with potential clinical applicability for myocardial viability determination.


Subject(s)
Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography , Magnetic Resonance Imaging, Cine , Myocardial Infarction/diagnostic imaging , Tomography, X-Ray Computed , Animals , Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography/methods , Magnetic Resonance Imaging, Cine/methods , Male , Myocardial Reperfusion Injury/diagnostic imaging , Rabbits , Technetium Tc 99m Sestamibi , Tomography, X-Ray Computed/methods
16.
Med Image Comput Comput Assist Interv ; 15(Pt 1): 107-14, 2012.
Article in English | MEDLINE | ID: mdl-23285541

ABSTRACT

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has become the de facto standard for current clinical therapy follow up evaluations. In pursuit of robust biomarkers for predicting early therapy response, an efficient marker quantification procedure is certainly a necessity. Among various PET derived markers, the clinical investigations indicated that the total lesion metabolic activity (TLA) of a tumor lesion has a good prognostic value in several longitudinal studies. We utilize a fuzzy multi-class modeling using a stochastic expectation maximization (SEM) algorithm to fit a finite mixture model (FMM) to the PET image. We then propose a direct estimation formula for TLA and SUVmean from this multi-class statistical model. In order to evaluate our proposition, a realistic liver lesion is simulated and reconstructed. All results were evaluated with reference to the ground truth knowledge. Our experimental study conveys that the proposed method is robust enough to handle background heterogeneities in realistic scenarios.


Subject(s)
Diagnostic Imaging/methods , Image Processing, Computer-Assisted/methods , Liver Neoplasms/pathology , Positron-Emission Tomography/methods , Algorithms , Biomarkers/metabolism , Computer Simulation , Fluorodeoxyglucose F18/pharmacology , Fuzzy Logic , Humans , Liver/pathology , Models, Statistical , Reproducibility of Results , Software , Stochastic Processes
17.
IEEE Trans Med Imaging ; 31(3): 599-612, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22049363

ABSTRACT

In emission tomography, image reconstruction and therefore also tracer development and diagnosis may benefit from the use of anatomical side information obtained with other imaging modalities in the same subject, as it helps to correct for the partial volume effect. One way to implement this, is to use the anatomical image for defining the a priori distribution in a maximum-a-posteriori (MAP) reconstruction algorithm. In this contribution, we use the PET-SORTEO Monte Carlo simulator to evaluate the quantitative accuracy reached by three different anatomical priors when reconstructing positron emission tomography (PET) brain images, using volumetric magnetic resonance imaging (MRI) to provide the anatomical information. The priors are: 1) a prior especially developed for FDG PET brain imaging, which relies on a segmentation of the MR-image (Baete , 2004); 2) the joint entropy-prior (Nuyts, 2007); 3) a prior that encourages smoothness within a position dependent neighborhood, computed from the MR-image. The latter prior was recently proposed by our group in (Vunckx and Nuyts, 2010), and was based on the prior presented by Bowsher (2004). The two latter priors do not rely on an explicit segmentation, which makes them more generally applicable than a segmentation-based prior. All three priors produced a compromise between noise and bias that was clearly better than that obtained with postsmoothed maximum likelihood expectation maximization (MLEM) or MAP with a relative difference prior. The performance of the joint entropy prior was slightly worse than that of the other two priors. The performance of the segmentation-based prior is quite sensitive to the accuracy of the segmentation. In contrast to the joint entropy-prior, the Bowsher-prior is easily tuned and does not suffer from convergence problems.


Subject(s)
Brain/anatomy & histology , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methods , Algorithms , Brain/diagnostic imaging , Brain/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Computer Simulation , Entropy , Humans , Monte Carlo Method , Phantoms, Imaging
18.
IEEE Trans Med Imaging ; 30(10): 1795-807, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21536518

ABSTRACT

The geometry of a single pinhole SPECT system with circular orbit can be uniquely determined from a measurement of three point sources, provided that at least two inter-point distances are known. In contrast, it has been shown mathematically that, for a multi-pinhole SPECT system with circular orbit, only two point sources are needed, and the knowledge of the distance between them is not required. In this paper, we report that this conclusion only holds if the motion of the camera is perfectly circular. In reality, the detector heads systematically slightly deviate from the circular orbit, which may introduce non-negligible bias in the estimated parameters and degrade the reconstructed image. An analytical linear model was extended to estimate the influence of both data noise and systematic deviations on the accuracy of the calibration and on the image quality of the reconstruction. It turns out that applying the knowledge of the distances greatly reduces the reconstruction error, especially in the presence of systematic deviations. In addition, we propose that instead of using the information about the distances between the point sources, it is more straightforward to use the knowledge about the distances between the pinhole apertures during multi-pinhole calibration. The two distance-fixing approaches yield similar reconstruction accuracy. Our theoretical results are supported by reconstruction images of a Jaszczak-type phantom scan.


Subject(s)
Image Processing, Computer-Assisted/methods , Tomography, Emission-Computed, Single-Photon/methods , Tomography, Emission-Computed, Single-Photon/standards , Algorithms , Calibration , Phantoms, Imaging , Reproducibility of Results , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon/instrumentation
19.
Mol Imaging Biol ; 13(5): 995-1002, 2011 Oct.
Article in English | MEDLINE | ID: mdl-20848227

ABSTRACT

PURPOSE: Early after therapy, 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) imaging is not always reliable due to the influx of inflammatory cells while apoptosis imaging offers a direct and early measurement of therapy effects. This study uses an improved apoptosis probe ((99m)Tc-hAnxA5) in combination with [(18)F]FDG imaging to evaluate therapy response. PROCEDURES: Daudi tumor tissue was implanted in the spleen of SCID mice. Treatment was performed with adriamycin and cyclophosphamide. Sequential [(18)F]FDG-positron emission tomography (PET) was acquired over 6 days and (99m)Tc-hAnxA5-SPECT was performed before and 1 day after therapy. RESULTS: On day 1, therapy induced apoptosis was visualized with (99m)Tc-hAnxA5 without a measurable change in [(18)F]FDG uptake. [(18)F]FDG uptake decreased significantly on day 3 and was even more pronounced on day 6. CONCLUSION: In this preclinical model, (99m)Tc-hAnxA5 imaging was able to detect apoptosis before metabolic changes were measured. These results confirm the value of apoptosis imaging for therapy response and give more insight in [(18)F]FDG imaging and its parameters to evaluate response.


Subject(s)
Apoptosis , Lymphoma/drug therapy , Animals , Cell Line, Tumor , Disease Models, Animal , Humans , Lymphoma/diagnostic imaging , Lymphoma/pathology , Magnetic Resonance Imaging , Mice , Mice, SCID , Positron-Emission Tomography , Tomography, Emission-Computed, Single-Photon
20.
IEEE Trans Med Imaging ; 29(12): 2038-52, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20667808

ABSTRACT

We have previously proposed a method to compare tomographic systems. It is assumed that each system acquires a tomographic scan of a certain tracer distribution in the same acquisition time. From this scan, each system is forced to reconstruct an image with a predefined spatial resolution. The system that can perform this task with the "most favorable" noise propagation is considered as the best system. The variance on pixel values or region-of-interest (ROI) values is used to assess the noise in the reconstructed image. In this paper, we extend this idea to compare the performance of parallel hole (PH) and rotating slat (RS) collimations. Two different analytical approaches were used to analyze the variance of the reconstructed pixel/ROI values. The first method is based on the filtered-backprojection (FBP) theory, and was applied to the central point of a uniform symmetrical phantom. It yields analytical expressions for the optimal collimator aperture and the corresponding variance of the reconstructed pixel values, but it can only be applied to highly symmetrical configurations. The second method is based on approximations for the Fisher information matrix. It provides numerical results, and it is more general and can be applied to nonsymmetrical objects and shift-variant tomographic systems. The collimations were compared for both planar imaging and volume imaging. The main results are as follows. 1) For cases where both methods are valid, they are in excellent agreement. 2a) The optimal collimator aperture varies linearly with the target resolution. 2b) For a fixed target resolution, the optimal collimator aperture depends on the collimator type and the imaging mode (planar or volume). 2c) The optimal aperture of PH is a factor of √2 larger than that of RS. 3a) The relative performance of the two collimators is determined by both the object size and the object-to-detector distance. 3b) Pixel variance and variances of ROIs with varying sizes yield very similar relative performance for RS versus PH.


Subject(s)
Image Processing, Computer-Assisted/methods , Models, Theoretical , Tomography, Emission-Computed, Single-Photon/instrumentation , Tomography, Emission-Computed, Single-Photon/methods , Algorithms , Analysis of Variance , Computer Simulation , Phantoms, Imaging , Reproducibility of Results
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