Cerebral [18 F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F]T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr⩾1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTE-related tauopathy in living subjects.

Dorsal striatal size, shape, and metabolic rate in never-medicated and previously medicated schizophrenics performing a verbal learning task.

BACKGROUND: Magnetic resonance imaging and positron emission tomography were used to study the size and metabolic rate of the caudate and the putamen in 18 patients with schizophrenia (n=16) or schizo-affective disorder (n=2) and 24 age- and sex-matched control subjects. METHODS: The patients were either never medicated (n=7) or drug free (n=11) for a median of 3 weeks. During uptake of fludeoxyglucose F 18, all patients performed a serial verbal learning test. Positron emission tomographic and magnetic resonance imaging scans were coregistered, and the caudate and the putamen were traced on the magnetic resonance image. RESULTS: The striatum had a significantly lower relative metabolic rate in schizophrenics than in controls. Never-medicated patients had lower metabolic rates in the right putamen (ventral part of the dorsal striatum) than previously medicated patients. The caudate was significantly smaller in never-medicated patients than in controls and largest in previously medicated patients. Patients with higher relative metabolic rates in the putamen scored higher on the Abnormal Involuntary Movements Scale. CONCLUSIONS: The findings are consistent with reports of striatal enlargement in previously medicated patients and size increases after neuroleptic treatment. Never-medicated patients, in contrast, had ventral striatal structures that were smaller and less active than those observed in controls and previously medicated patients.

Precise fusion of MRI and dual energy 111In WBC/99mTc HDP SPECT/CT in the diabetic foot using companion CT: an example of SPECT/MRI imaging.

AIM: The purpose of our study was to correctly fuse MRI and SPECT ¹¹¹In WBC and 99m Tc HDP images using companion CT images. The fused images could be used to assess proper surgical approach in treatment of the diabetic foot. METHODS: Nine patients who had dual energy ¹¹¹In WBC/ 99m Tc HDP SPECT/CT and MRI studies within a week were investigated in an ongoing project. A GE Infinia SPECT/CT camera and Siemens MAGNETOM 1.5T MR system were used in this study. First, the MRI and corresponding CT images were coregistrated using a transformation based on normalized mutual information. The transformation was saved and used for MRI and ¹¹¹In WBC/ 99m Tc HDP SPECT fusion. A Jaszczak phantom study was also performed in order to estimate accuracy of MRI/ SPECT fusion. RESULTS: The Jaszczak phantom study with 3.7 MBq ¹¹¹In hot sphere showed that MRI/SPECT alignment using the approach described above produced registration with 0.7 ± 0.4 mm accuracy in all three dimensions (3D). The nine clinical cases were visually evaluated and showed 1-2 mm 3D fusion accuracy. MRI provides almost perfect anatomy of soft tissue and bony structures but it may exaggerate the extent of infection. ¹¹¹In WBC/99m Tc HDP SPECT imaging is more accurate for infection detection but lacks anatomical reference. Combination of these images proved an essential adjunct to diagnosis. A clinical utility of the approach is illustrated in two clinical examples. CONCLUSION: The CT in dual energy ¹¹¹In WBC/99m Tc HDP SPECT/CT studies can be used to accurately fuse and compare ¹¹¹In WBC/99m Tc HDP SPECT and MRI images of the diabetic foot. This can significantly help in conservative treatment planning and limb salvage procedures in treatment of diabetic foot infections.

Three-window transformation cross-talk correction for simultaneous dual-isotope imaging.

UNLABELLED: We developed and tested a new transformation cross-talk correction method for simultaneous dual-isotope SPECT imaging, which uses information from three energy windows in a simultaneous 18F/99mTc cardiac phantom study. METHODS: The method combines the previously reported "three-window" technique and transformation cross-talk correction methods. In the three-window technique, the images from the third energy "scatter" window are usually multiplied by a constant factor to obtain the estimates of the cross-talk. However, such an approach neglects differences in the spatial distribution between cross-talk photons in different energy windows. The transformation method is based on the assumption that the transformations, which convert the images from one energy window into the other energy windows, are known. These transformations were found by measuring the point-spread functions in different energy windows for both isotopes in water. The transformation method takes into account the different spatial distributions of the primary and scatter cross-talk photons in the different energy windows. Here, we are assuming that the imaging system and the image transformations between different energy windows are shift-invariant and linear. Thus, the new method is described by two convolution equations applied in frequency space. In addition to the cross-talk correction, the restoration filters were also applied to the resulting corrected images. The new method was performed on the simultaneous 18F/99mTc cardiac phantom study. Three separate studies were acquired in our phantom study: two single-isotope studies and one dual-isotope study. The single-isotope images were used as references. The contrast between the left ventricle cavity and the myocardium was used in transaxial slices as a parameter to evaluate results of the dual-isotope correction method with restoration. RESULTS: The contrast improvement in the dual-isotope corrected images in both energy windows, i.e., the 99mTc primary window (140 keV) and the 18F primary window (511 keV), was significant. The corrected 511-keV, dual-isotope image had a contrast of 0.74 compared to 0.60, which was the value in the noncorrected dual-isotope image. The improvement of the contrast in the corrected, dual-isotope 511-keV image was exclusively a result of the restoration correction. The restoration-corrected, 511-keV, single-isotope 18F image had the same contrast (0.74). For the dual-isotope, 140-keV transaxial slice, first, the contrast improved from 0.78 to 0.85 after cross-talk correction, and, then, it finally reached 0.92 after additional restoration correction. The contrast in the 140-keV, single-isotope 99mTc image after restoration correction improved from 0.87 to 0.95. CONCLUSION: The three-window transformation dual-isotope correction method with restoration significantly improves the contrast between the left ventricle cavity and the myocardium of the simultaneous 18F/99mTc SPECT imaging.

Investigation of causes of geometric distortion in 180 degrees and 360 degrees angular sampling in SPECT.

To investigate geometric distortion when 180 degrees or 360 degrees angular sampling techniques are used in single photon emission computed tomography (SPECT), a study of point sources imaged at different positions in a water filled cylindrical phantom, and reconstructed using filtered back projection, was conducted. A simulation study, based upon a serial model of the system point spread function (PSF), was used to investigate the contributions of attenuation, spatial resolution and scatter on distortion of the reconstructed PSFs. To study the geometric distortion in transverse (x-y plane), coronal (x-z plane), and sagittal (y-z plane) sections, the ratios of the full widths at half maximum (FWHM) and full widths at tenth maximum (FWTM) in the x/y, x/z, and y/z directions were calculated for the real and simulated PSFs. These results showed that, in an attenuating medium, there is more distortion of point sources into ovals for 180 degrees than for 360 degrees sampling. The simulation study indicated that the primary cause of geometrical distortion in SPECT studies, is the inconsistency of projections due to variable attenuation and spatial resolution. The impact of scatter on geometric distortion was small as measured by the ratios of FWHMs and FWTMs for PSFs. Attenuation correction applied to acquired PSFs significantly reduced geometric distortion in both 180 degrees and 360 degrees studies. To investigate distortion in extended objects, an Iowa heart phantom was placed inside an Alderson body phantom and 201Tl heart SPECT studies acquired. The phantom images confirmed the conclusion that in transverse sections of 360 degrees studies with arithmetic averaging of opposite views, geometric distortion is reduced compared to 180 degrees. The coronal and sagittal sections were equally distorted in both, the 180 degrees and 360 degrees studies, and the 180 degrees studies yielded better contrast.

A new dual-isotope convolution cross-talk correction method: a Tl-201/Tc-99m SPECT cardiac phantom study.

Simultaneous dual-isotope SPECT imaging provides a clear advantage in situations where two concurrent metabolic, anatomic, or background measurements are desired. It obviates the need for two separate imaging sessions, reduces patient motion problems, and provides exact image registration between images. However, a potential limitation of dual-isotope SPECT imaging is contribution of scattered and primary photons from one radionuclide into the second radionuclide's photopeak energy window, referred to here as cross-talk. Cross-talk in both photopeak energy windows can significantly degrade image quality, resolution, and quantitation to an unacceptable level. Simple cross-talk correction method used in dual-radionuclide in vitro counting, even applied on a pixel-by-pixel basis, does not account for the differences in spatial distribution of the photopeak and cross-talk photons. Here a new convolution cross-talk correction method is presented. The convolution filters are derived from point response functions (PRFs) for Tc-99m and Tl-201 point sources. Three separate acquisitions were performed, each with two 20% wide energy windows, one centered at 140 keV and another at 70 keV. The first acquisition was done with Tc-99m solution only, the second with Tl-201 solution only, and the third with a mixture of Tc-99m and Tl-201. The nonuniform RH-2 thorax-heart phantom was used to test a new correction technique. The main difficulty and limitation of the convolution correction approach is caused by the variation in PRF as a function of depth. Thus, average PRF should be used in the creation of an approximative filter.(ABSTRACT TRUNCATED AT 250 WORDS)

Two new experimental methods of calculating scatter fraction as a function of depth in scattering media: a comparison study.

Two new experimental methods of calculating scatter fraction (SF), as a function of depth, are presented and used in a comparison study. These methods are based on the assumptions that the total point spread function (psft) consists of geometrical (psfg) and scattering (psfs) components, and that the psft and its components are radially symmetric functions. Both methods assume that psfg is a two-dimensional (2-D) Gaussian function. The first proposed method is based on the serial model of the psft. According to the serial model, psfs is also a 2-D Gaussian function. However, the second method is based on the assumption that the psfs is a monoexponential function. Thus the main difference between these two experimental methods is the way in which the psfs is treated. Published data obtained by Monte Carlo simulations compared to the new experimental results shows that for depths less than 5 cm, both new methods yield smaller values for scatter fraction than Monte Carlo simulation or the subtraction method. However, for depths from 5 to 20 cm, the results of these two new methods were very close to the values obtained by both the Monte Carlo simulation and the subtraction method. These two methods have allowed assessment of the scatter fraction with higher accuracy and reliability and reporting data concludes that the new methods are less error sensitive than the subtraction method.

Improvement of the fluorine-18 fluorodeoxyglucose images in simultaneous F-18 FDG/Tc-99m collimated spect imaging.

Collimated F-18 FDG SPECT imaging has been shown to be an acceptable alternative to F-18 FDG PET imaging for evaluating injured but viable myocardium. Ultra-energy (UHE) imaging is usually performed in simultaneous F-18 FDG/Tc-99m MIBI studies. The main limitations of this technique are degradation of the Tc-99m MIBI images due to F-18 downscatter to the Tc-99m window, and loss of resolution in Tc-99m images caused by using a UHE rather than a low-energy collimator. The quality of F-18 images has not been addressed. In our clinical and phantom studies we have found that F-18 images are inferior to simultaneously acquired Tc-99m MIBI images. This paper compares two correction methods for F-18 FDG images in a realistic cardiac phantom study. One approach is subtractive scatter correction, which employs a third 410 keV energy window image to estimate scatter. The other approach is based on restoration. The phantom acquisition was performed with 7.2 MBq of F-18 and 22.2 MBq of Tc-99m injected into the left ventricular (LV) wall. Three inserts, 3 cm, 2 cm, and 1 cm in diameter, were placed in the LV wall to simulate infarcts. Circumferential profiles were drawn from three successive short-axis slices and compared with true phantom data. The differences were calculated as root-mean-square error (rmse). Scatter correction improved rmse only 4.5 +/- 0.3%, while restoration improved rmse 16.1 +/- 0.4%, when compared with raw data. The same differences, measured as rmse, were 9.5 +/- 0.5, 6.8 +/- 0.4, and 5.1 +/- 0.5 for raw, scatter corrected, and restored F-18 data, respectively, when compared with Tc-99m window 140 keV data. The amount of noise, measured as root-mean-square % (rms%) was 5.3 +/- 0.5% for the Tc-99m image, 4.9 +/- 0.7% for the F-18 restored image, 6.2 +/- 0.6% for the raw F-18 image, and 6.5 +/- 0.9% for the scatter corrected F-18 image. The contrast measured for 2 cm and 3 cm inserts was 0.17 +/- 0.07 and 0.26 +/- 0.06 for F-18 raw data, 0.19 +/- 0.08 and 0.29 +/- 0.06 for the scatter corrected F-18 image, and 0.28 +/- 0.06 and 0.43 +/- 0.07 for the restored F-18 image. The contrast was 0.20 +/- 0.07 and 0.46 +/- 0.05 for the Tc-99m 140 keV window image. The restoration approach provided F-18 images of better contrast and detectibility than uncorrected or scatter corrected F-18 images. Restored F-18 images match better with the simultaneously acquired Tc-99m images.

Enhanced cross-talk correction technique for simultaneous dual-isotope imaging: a TL-201/Tc-99m myocardial perfusion SPECT dog study.

A newly developed cross-talk correction method for simultaneous dual-isotope SPECT imaging was tested in a canine model. The method is based on the assumption that the transformations, which modify the primary energy window images into the scatter images as viewed in the other energy windows, are known. These transformations were found by measuring the point spread functions (PSFs) in two different energy windows for both isotopes in water. The dual-isotope correction method is described by two convolution equations which were applied in frequency space. The equations take into account the different spatial distributions of the primary and scatter cross-talk photons. The new enhancement of the method was in applying restoration filters to the resulting corrected images. Three separate studies were acquired in our dog study: two single-isotope and one dual-isotope study. The single isotope images were used as references. The contrast between the left ventricle cavity (LVC) and the myocardium was used in transaxial and short-axis slices as a parameter to evaluate results of dual-isotope correction method with restoration. The change in contrast in the dual-isotope corrected images in both energy windows, i.e., Tc-99m primary window (140 keV) and Tl-201 primary window (70 keV), was significant. The only exception was for the short-axis Tc-99m window images. The corrected 140 keV dual-isotope short-axis slice had the contrast of 0.60 vs 0.58, which was the value in the noncorrected dual-isotope short-axis slice. For dual-isotope 140 keV transaxial slice, the contrast changed from 0.72 to 0.82 after correction. In comparison, for single-isotope Tc-99m 140 keV transaxial slice, contrast changed from 0.62 to 0.84 after restoration correction. There was less change in contrast in the short-axis Tc-99m 140 keV slice, i.e., from 0.56 to 0.61. In the Tl-201 primary window for the transaxial slices the improvement of contrast was from 0.38 to 0.64, and for short-axis slices from 0.22 to 0.32 after correction. In the same 70 keV energy window for single-isotope Tl-201 images, contrast improved from 0.61 to 0.69 and from 0.35 to 0.38 for transaxial and short-axis slice, respectively, after applying restoration correction. In conclusion, the presented dual-isotope correction method with restoration improves the quality of the simultaneous rest Tl-201/stress Tc-99m sestamibi SPECT imaging.

Comparison of 360 degrees and 180 degrees data collection in SPECT imaging.

The problem of using 360 degrees or 180 degrees data sampling techniques in transaxial SPECT imaging is still to be solved. A theoretical point source study for an ideal response detector has shown, for objects which are close enough to the origin of the reconstructed area, that there are significant differences between sections obtained by different sampling methods. A computer simulation study of line sources in a homogeneous attenuated medium has confirmed the results of clinical studies in which significant image distortion has been observed in 180 degrees sections but not in 360 degrees reconstructed images.

Extended three-compartment model for the transport and distribution of Hippuran.

The distribution and transport of Hippuran is discussed. The activity leaving both kidneys has been calculated and compared with the bladder activity. It is shown that the Impulse Response Function of the ureter and bladder may be obtained by deconvolution, and data are presented relating to studies on one patient.

Comparison of correction techniques for simultaneous 201Tl/99mTc myocardial perfusion SPECT imaging: a dog study.

We compared two correction methods for simultaneous 201Tl/99mTc dual-isotope single-photon emission computed tomography (SPECT). Both approaches use the information from the third energy window placed between the photopeak windows of the 201Tl and 99mTc. The first approach, described by Moore et al, corrects only for the contribution of the 99mTc to the 201Tl primary 70 keV window. We developed the three-window transformation dual isotope correction method, which is a simultaneous cross-talk correction. The two correction methods were compared in a simultaneous 201Tl/99mTc sestamibi cardiac dog study. Three separate acquisitions were performed in this dog study: two single-isotope and one dual-isotope acquisition. The 201Tl single-isotope images were used as references. The total number of counts, and the contrast between the left ventricular cavity (LVC) and the myocardium, were used in 70 keV short axis slices as parameters for evaluating the results of the dual-isotope correction methods. Three consecutive short-axis slices were used to calculate averaged contrast and the averaged total number of counts. The total number of the counts was 667000+/-500 and 414500+/-400 counts for the dual isotope (201Tl+/-99mTc) and single-isotope (201Tl-only) 70 keV images, respectively. The corrected dual-isotope images had 514700+/-700 and 368000+/-600 counts for Moore's correction and our approach, respectively. Moore's method improved contrast in the dual isotope 70 keV image to 0.14+/-0.03 from 0.11+/-0.02, which was the value in the 70 keV non-corrected dual-isotope image. Our method improved the same contrast to 0.22+/-0.03. The contrast in the 201Tl single-isotope 70 keV image was 0.28+/-0.02. Both methods improved the 70 keV dual-isotope images. However, our approach provided slightly better images than Moore's correction when compared with 201Tl-only 70 keV images.

A transformation cross-talk technique for simultaneous dual radionuclide imaging: a myocardial perfusion 201Tl/99Tcm sestamibi dog SPECT study.

We have developed a novel transformation method for the correction of cross-talk in simultaneous dual radionuclide single photon emission CT (SPECT) imaging. It is based on the assumption that the transformations, which transform the primary energy window images into the scatter images as viewed in the other energy windows, are known. The method was tested on a dog model. These transformations were found by measuring the point response functions (prf) in different energy windows for both radionuclides in water. The dual radionuclide correction method described takes into account the different spatial distributions of the primary and scatter cross-talk photons in different energy windows. This method also includes the sequential application of restoration filters to the resulting cross-talk corrected images. We used a dog model in three separate studies: two single radionuclide studies used as references and one dual radionuclide study. Contrast between the left ventricular cavity (LVC) and the myocardium was used in horizontal long axis (HLA) slices as a parameter to evaluate the results of the dual radionuclide correction method with restoration. The increase of the contrast in the dual radionuclide corrected images in both energy windows, i.e. 201Tl primary window (70 keV) and 99Tcm primary window (140 keV), was significant. The cross-talk corrected 70 keV dual radionuclide HLA slice had a contrast of 0.62 compared with 0.35, which was the value in the non-corrected dual radionuclide HLA slice. Restoration improved the contrast to 0.68. In the single radionuclide 201Tl image, the same contrast was 0.59, improving to 0.70 after restoration. For the dual radionuclide 140 keV HLA slice, the contrast increased from 0.69 to 0.76 after cross-talk correction. Additional increase of the contrast to 0.83 resulted from restoration filtering. In the single radionuclide 99Tcm sestamibi 140 keV HLA slice the improvement of contrast was from 0.63 to 0.86 as a result of the restoration. The transformation three-window, dual radionuclide correction method with restoration improves the quality of the simultaneous rest 201Tl/stress 99Tcm sestamibi SPECT imaging.

A stochastic approach to tracer kinetics.

The single compartment well-mixed model ( SCWMM ) which has been used in almost all dynamic studies in nuclear medicine is, in fact , strictly accurate only in the case of a steady state obtained by means of constant administration of long-lived isotopes. That is the reason why SCWMM is not a good predictor of the behaviour of short-lived isotopes and why the distribution and transport of short- and long-lived isotopes in various situations has not yet been discussed in general terms. The aim of this paper is to do that by means of a more general stochastic approach. This more general approach takes into account the distribution and transport of tracer in the system, not requiring a hypothesis of good mixing and providing a possibility of making corrections due to decay in the case of short-lived isotopes studies.

Non-uniform attenuation correction in SPET using a modified conjugate gradient reconstruction method.

We describe a non-uniform iterative attentuation correction method for single photon emission tomography (SPET) which uses transmission data. The method was derived using the general inverse problem theory. A cost functional which includes noise was derived and minimized using a weighted-least-square maximum a posteriori conjugate gradient (CG) method. The Hessian of the cost functional was modified by adding a noise term. The a priori value of the model data vector was neglected. The method was tested in a clinical cardiac SPET perfusion study. Prior to the emission scan, blank and transmission scans were acquired and used to obtain the non-uniform map of linear attenuation coefficients. The results of the study show that the new iterative method has a slightly better convergence rate than the standard CG method. Also, the corrected emission slices obtained by the new method were less noisy. Noise was measured as rms% and was reduced by a factor of 2.3 for the transmission scans and by a factor of 1.9 for the emission scans when reconstructed with the new method compared to the CG method. The new method provides a stable solution, whereas the standard CG method, for higher iterative steps, diverges. There is potential for improvement in the approach described here.