scholarly journals Development of a High-resolution SSR-SPECT System for Preclinical Imaging and Neuroimaging

Author(s):  
Annunziata D'Elia ◽  
Andrea Soluri ◽  
Filippo Galli ◽  
Sara Schiavi ◽  
Giselda De Silva ◽  
...  

Abstract The utility of animal models in preclinical research has been increasing by the availability of methods for in vivo imaging. In particular, techniques like single photon emission computed tomography (SPECT) show high potential, which is usually limited by spatial resolution. This represents an important parameter influencing scanner design, given the small size of the anatomical structures to be investigated. The purpose of the present work was to assess the performance of a scintigraphic system with improved spatial resolution based on our previous detector by applying the Super Spatial Resolution (SSR). Our dual-head SPECT system is composed of gamma cameras based on the Hamamatsu H13700 position-sensitive photomultiplier tube (PSPMT). In each detector head, the PSPMT is coupled to a 28×28 array of CRY018 scintillation crystals. The pure Tungsten parallel square hole collimator ensures the position sensitivity, and a dedicated resistive chain readout so as an ADC board have been proprietary designed. To finalize the mechanical development of the SSR-SPECT system several tests were carried out. Based on the results obtained in the test phase, a partial review of the mechanical design was performed. Then a dedicated machine handling software was developed, and in particular, a kinematic software debugging and testing was assessed. Finally, several experiments were carried out by using Derenzo phantoms and capillaries filled with radioactive sources. Finally, the performance of our system was evaluated performing small animal imaging studies. The SPECT spatial resolution was experimentally determined to be about 1.6 mm. We reach a resolution of 1.18 mm by applying the SSR based on two images. The results of this study demonstrated the good capability of the system as a suitable tool for preclinical imaging especially in fields like neuroscience for the study of small brain structures.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jan P. Janssen ◽  
Jan V. Hoffmann ◽  
Takayuki Kanno ◽  
Naoko Nose ◽  
Jan-Peter Grunz ◽  
...  

Abstract We aimed to investigate the image quality of the U-SPECT5/CT E-Class a micro single-photon emission computed tomography (SPECT) system with two large stationary detectors for visualization of rat hearts and bones using clinically available 99mTc-labelled tracers. Sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR) of the small-animal SPECT scanner were investigated in phantom studies using an ultra-high-resolution rat and mouse multi-pinhole collimator (UHR-RM). Point source, hot-rod, and uniform phantoms with 99mTc-solution were scanned for high-count performance assessment and count levels equal to animal scans, respectively. Reconstruction was performed using the similarity-regulated ordered-subsets expectation maximization (SROSEM) algorithm with Gaussian smoothing. Rats were injected with ~ 100 MBq [99mTc]Tc-MIBI or ~ 150 MBq [99mTc]Tc-HMDP and received multi-frame micro-SPECT imaging after tracer distribution. Animal scans were reconstructed for three different acquisition times and post-processed with different sized Gaussian filters. Following reconstruction, CNR was calculated and image quality evaluated by three independent readers on a five-point scale from 1 = “very poor” to 5 = “very good”. Point source sensitivity was 567 cps/MBq and radioactive rods as small as 1.2 mm were resolved with the UHR-RM collimator. Collimator-dependent uniformity was 55.5%. Phantom CNR improved with increasing rod size, filter size and activity concentration. Left ventricle and bone structures were successfully visualized in rat experiments. Image quality was strongly affected by the extent of post-filtering, whereas scan time did not have substantial influence on visual assessment. Good image quality was achieved for resolution range greater than 1.8 mm in bone and 2.8 mm in heart. The recently introduced small animal SPECT system with two stationary detectors and UHR-RM collimator is capable to provide excellent image quality in heart and bone scans in a rat using standardized reconstruction parameters and appropriate post-filtering. However, there are still challenges in achieving maximum system resolution in the sub-millimeter range with in vivo settings under limited injection dose and acquisition time.


2020 ◽  
Author(s):  
Jan V Hoffmann ◽  
Jan P Janssen ◽  
Takayuki Kanno ◽  
Takayuki Shibutani ◽  
Masahisa Onoguchi ◽  
...  

Abstract Background: Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. These systems benefit from less labour-intensive maintenance and quality control as fewer prone parts are moving, higher accuracy for focused scans and maintaining high resolution with increased sensitivity due to focused pinholes on the field of view. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector-configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT+).Methods: The new U-SPECT5-E with two stationary detectors was used for acquiring data with 99mTc-filled point source, hot-rod and uniformity phantoms to analyse sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR). Three dedicated multi-pinhole mouse collimators with 75 pinholes each and 0.25-, 0.60- and 1.00-mm pinholes for extra ultra-high resolution (XUHR-M), general-purpose (GP-M) and ultra-high sensitivity (UHS-M) imaging were examined. For CNR analysis, four different activity ranges representing low- and high-count settings were investigated for all three collimators. The experiments for the performance assessment were repeated with the same GP-M collimator in the three-detector U-SPECT+ for comparison. Results: Peak sensitivity was 237 cps/MBq (XUHR-M), 847 cps/MBq (GP-M), 2054 cps/MBq (UHS-M) for U-SPECT5-E and 1710 cps/MBq (GP-M) for U-SPECT+. In the visually analysed sections of the reconstructed mini Derenzo phantom, rods as small as 0.35 mm (XUHR-M), 0.50 mm (GP-M) for the two-detector as well as the three-detector SPECT and 0.75 mm (UHS-M) were resolved. Uniformity for maximum resolution recorded 40.7% (XUHR-M), 29.1% (GP-M, U-SPECT5-E), 16.3% (GP-M, U-SPECT+) and 23.0% (UHS-M), respectively. UHS-M reached highest CNR values for low-count images; for rods smaller than 0.45 mm, acceptable CNR was only achieved by XUHR-M. GP-M was superior for imaging rods sized from 0.60-1.50 mm for intermediate activity concentrations. U-SPECT5-E and U-SPECT+ both provided comparable CNR.Conclusions: While uniformity and sensitivity are negatively affected by the absence of a third detector, the investigated U-SPECT5-E system with two stationary detectors delivers excellent spatial resolution and CNR comparable to the performance of an established three-detector-setup.


2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Jan V. Hoffmann ◽  
Jan P. Janssen ◽  
Takayuki Kanno ◽  
Takayuki Shibutani ◽  
Masahisa Onoguchi ◽  
...  

Abstract Background Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. These systems benefit from less labour-intensive maintenance and quality control as fewer prone parts are moving, higher accuracy for focused scans and maintaining high resolution with increased sensitivity due to focused pinholes on the field of view. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT+). Methods The new U-SPECT5-E with two stationary detectors was used for acquiring data with 99mTc-filled point source, hot-rod and uniformity phantoms to analyse sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR). Three dedicated multi-pinhole mouse collimators with 75 pinholes each and 0.25-, 0.60- and 1.00-mm pinholes for extra ultra-high resolution (XUHR-M), general-purpose (GP-M) and ultra-high sensitivity (UHS-M) imaging were examined. For CNR analysis, four different activity ranges representing low- and high-count settings were investigated for all three collimators. The experiments for the performance assessment were repeated with the same GP-M collimator in the three-detector U-SPECT+ for comparison. Results Peak sensitivity was 237 cps/MBq (XUHR-M), 847 cps/MBq (GP-M), 2054 cps/MBq (UHS-M) for U-SPECT5-E and 1710 cps/MBq (GP-M) for U-SPECT+. In the visually analysed sections of the reconstructed mini Derenzo phantoms, rods as small as 0.35 mm (XUHR-M), 0.50 mm (GP-M) for the two-detector as well as the three-detector SPECT and 0.75 mm (UHS-M) were resolved. Uniformity for maximum resolution recorded 40.7% (XUHR-M), 29.1% (GP-M, U-SPECT5-E), 16.3% (GP-M, U-SPECT+) and 23.0% (UHS-M), respectively. UHS-M reached highest CNR values for low-count images; for rods smaller than 0.45 mm, acceptable CNR was only achieved by XUHR-M. GP-M was superior for imaging rods sized from 0.60 to 1.50 mm for intermediate activity concentrations. U-SPECT5-E and U-SPECT+ both provided comparable CNR. Conclusions While uniformity and sensitivity are negatively affected by the absence of a third detector, the investigated U-SPECT5-E system with two stationary detectors delivers excellent spatial resolution and CNR comparable to the performance of an established three-detector-setup.


2020 ◽  
Author(s):  
Jan V Hoffmann ◽  
Jan P Janssen ◽  
Takayuki Kanno ◽  
Takayuki Shibutani ◽  
Masahisa Onoguchi ◽  
...  

Abstract Purpose Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector-configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT+). Methods The new U-SPECT5-E with two stationary detectors was used for acquiring data with 99mTc-filled point source, hot-rod and uniformity phantoms to analyse sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR). Three dedicated multi-pinhole mouse collimators with 75 pinholes each and 0.25-, 0.60- and 1.00-mm pinholes for extra ultra-high resolution (XUHR-M), general-purpose (GP-M) and ultra-high sensitivity (UHS-M) imaging were examined. For CNR analysis, four different activity ranges representing low- and high-count settings were investigated for all three collimators. The experiments for the performance assessment were repeated with the same GP-M collimator in the three-detector U-SPECT+ for comparison. Results Peak sensitivity was 237 cps/MBq (XUHR-M), 847 cps/MBq (GP-M), 2054 cps/MBq (UHS-M) for U-SPECT5-E and 1710 cps/MBq (GP-M) for U-SPECT+. Resolution in the visually analysed sections of the reconstructed hot-rod phantom was 0.35 mm (XUHR-M), 0.50 mm (GP-M) for the two-detector as well as the three-detector SPECT and 0.75 mm (UHS-M). Uniformity for maximum resolution recorded 40.7% (XUHR-M), 29.1% (GP-M, U-SPECT5-E), 16.3% (GP-M, U-SPECT+) and 23.0% (UHS-M), respectively. UHS-M reached highest CNR values for low-count images; for rods smaller than 0.45 mm, acceptable CNR was only achieved by XUHR-M. GP-M was superior for imaging rods sized from 0.60–1.50 mm for intermediate activity concentrations. U-SPECT5-E and U-SPECT+ both provided comparable CNR. Conclusions While uniformity and sensitivity are negatively affected by the absence of a third detector, the investigated U-SPECT5-E system with two stationary detectors delivers excellent spatial resolution and CNR comparable to the performance of an established three-detector-setup.


2021 ◽  
Vol 15 ◽  
Author(s):  
Susanne Nikolaus ◽  
Hans-Jörg Wittsack ◽  
Christina Antke ◽  
Markus Beu ◽  
Hubertus Hautzel ◽  
...  

Purpose: The 5-HT2A receptor (R) is known to modulate dopamine (DA) release in the mammalian brain. Altanserin (ALT) and 2,5-dimethoxy-4-iodoamphetamine (DOI) act as 5-HT2AR antagonist and agonist, respectively. In the present study, we assessed the effects of ALT and DOI on motor and exploratory behaviors and on D2/3R binding in the rat brain with in vivo imaging methods.Methods: D2/3R binding was determined after systemic application of ALT (10 mg/kg) or DOI (0.5 mg/kg) and the respective vehicles [dimethyl sulfoxide (DMSO) and 0.9% saline (SAL)] with [123I]IBZM as a single-photon emission computed tomography (SPECT) radioligand. Anatomical information for the delineation of the target regions was obtained with dedicated small animal MRI. Immediately after 5-HT2AR antagonistic or agonistic treatment, motor/exploratory behaviors were assessed for 45 (ALT) or 30 min (DOI) in an open field. Additional rats underwent behavioral measurements after injection of DMSO or SAL.Results: ALT increased D2/3R binding in the ventral hippocampus relative to vehicle, while DOI augmented D2/3R binding in caudate putamen, frontal cortex, motor cortex, and ventral hippocampus. The 5-HT2AR agonist as well as antagonist decreased parameters of motor activity and active exploration. However, ALT, in contrast to DOI, decreased explorative head–shoulder motility and increased sitting.Conclusions: The regional increases of D2/3R binding after ALT and DOI (90 and 75 min post-challenge) may be conceived to reflect decreases of synaptic DA. The reductions of motor/exploratory activities (min 1–45 and min 1–30 after challenge with ALT and DOI, respectively) contrast the regional reductions of D2/3R binding, as they indicate elevated DA levels at the time of behavioral measurements. It may be concluded that ALT and DOI modulate DA in the individual regions of the nigrostriatal and mesolimbocortical pathways differentially and in a time-dependent fashion.


Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 463 ◽  
Author(s):  
Patricia E. Edem ◽  
Jesper T. Jørgensen ◽  
Kamilla Nørregaard ◽  
Rafaella Rossin ◽  
Abdolreza Yazdani ◽  
...  

The bioorthogonal reaction between a tetrazine and strained trans-cyclooctene (TCO) has garnered success in pretargeted imaging. This reaction was first validated in nuclear imaging using an 111In-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-linked bispyridyl tetrazine (Tz) ([111In]In-DOTA-PEG11-Tz) and a TCO functionalized CC49 antibody. Given the initial success of this Tz, it has been paired with TCO functionalized small molecules, diabodies, and affibodies for in vivo pretargeted studies. Furthermore, the single photon emission tomography (SPECT) radionuclide, 111In, has been replaced with the β-emitter, 177Lu and α-emitter, 212Pb, both yielding the opportunity for targeted radiotherapy. Despite use of the ‘universal chelator’, DOTA, there is yet to be an analogue suitable for positron emission tomography (PET) using a widely available radionuclide. Here, a 68Ga-labeled variant ([68Ga]Ga-DOTA-PEG11-Tz) was developed and evaluated using two different in vivo pretargeting systems (Aln-TCO and TCO-CC49). Small animal imaging and ex vivo biodistribution studies were performed and revealed target specific uptake of [68Ga]Ga-DOTA-PEG11-Tz in the bone (3.7 %ID/g, knee) in mice pretreated with Aln-TCO and tumor specific uptake (5.8 %ID/g) with TCO-CC49 in mice bearing LS174 xenografts. Given the results of this study, [68Ga]Ga-DOTA-PEG11-Tz can serve as an alternative to [111In]In-DOTA-PEG11-Tz.


2020 ◽  
Vol 13 (10) ◽  
pp. 272
Author(s):  
Falco Reissig ◽  
David Bauer ◽  
Martin Ullrich ◽  
Martin Kreller ◽  
Jens Pietzsch ◽  
...  

Barium-131 is a single photon emission computed tomography (SPECT)-compatible radionuclide for nuclear medicine and a promising diagnostic match for radium-223/-224. Herein, we report on the sufficient production route 133Cs(p,3n)131Ba by using 27.5 MeV proton beams. An average of 190 MBq barium-131 per irradiation was obtained. The SR Resin-based purification process led to barium-131 in high radiochemical purity. An isotopic impurity of 0.01% barium-133 was detectable. For the first time, radiolabeling of the ligand macropa with barium-131 was performed. Radiolabeling methods under mild conditions and reaction controls based on TLC systems were successfully applied. Small animal SPECT/ computed tomography (CT) measurements and biodistribution studies were performed using [131Ba]Ba(NO3)2 as reference and 131Ba-labeled macropa in healthy mice for the first time. Biodistribution studies revealed the expected rapid bone uptake of [131Ba]Ba2+, whereas 131Ba-labeled macropa showed a fast clearance from the blood, thereby showing a significantly (p < 0.001) lower accumulation in the bone. We conclude that barium-131 is a promising SPECT radionuclide and delivers appropriate imaging qualities in small animals. Furthermore, the relative stability of the 131Ba-labeled macropa complex in vivo forms the basis for the development of sufficient new chelators, especially for radium isotopes. Thereby, barium-131 will attain its goal as a diagnostic match to the alpha emitters radium-223 and radium-224.


2020 ◽  
Author(s):  
Takayuki Shibutani ◽  
Masahisa Onoguchi ◽  
Hiroto Yoneyama ◽  
Takahiro Konishi ◽  
Kenichi Nakajima

Abstract Background A new low-energy high-resolution-sensitivity (LEHRS) collimator was developed by General Electric Healthcare. SwiftScan planar and SPECT system using LEHRS collimator were formulated to achieve the low-dose and/or short-term acquisition. We demonstrated the performance of SwiftScan planar and SPECT system with LEHRS collimator using phantoms. Methods Line source, cylindrical and flat plastic dish phantoms were used to evaluate the performance of planar and SPECT images for four patterns of Siemens LEHR, GE LEHR, GE LEHRS and SwiftScan using two SPECT-CT scanners. Each phantom was filled with 99mTc solution, and the spatial resolution, sensitivity and image uniformity were calculated from the planar and SPECT data. Results The full-width at half maximum (FWHM) values as system spatial resolution of Siemens LEHR, GE LEHR and GE LEHRS were 7.3, 7.5 and 7.3 mm, respectively. GE LEHRS showed the lower FWHM value by increasing the blend ratio in Clarity 2D processing. The system sensitivities of Siemens LEHR, GE LEHR and GE LEHRS were 88.4, 67.6 and 89.8 cps/MBq, respectively. The system sensitivity of GE LEHRS increased by approximately 30% compared with that of GE LEHR and was similar to that of Siemens LEHR. The FWHM values of SPECT with an FBP method were 10.3, 10.4, 10.4 and 10.3 mm (p = n.s.). The FWHM values of the OSEM method were better with an increase in iteration values. The differential uniformities of Siemens LEHR, GE LEHR, GE LEHRS and GE SwiftScan were 15.3%, 15.1%, 15.4% and 14.6%, respectively, using the FBP method. The differential uniformity of OSEM method was higher with an increase in iteration value. Conclusion The SwiftScan planar and SPECT have a high sensitivity while maintaining the spatial resolution compared with the conventional system.


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