The clinical utilities of multi-pinhole single photon emission computed tomography

Single photon emission computed tomography (SPECT) is an important imaging modality for various applications in nuclear medicine. The use of multi-pinhole (MPH) collimators can provide superior resolution-sensitivity trade-off when imaging small field-of-view compared to conventional parallel-hole and fan-beam collimators. Besides the very successful application in small animal imaging, there has been a resurgence of the use of MPH collimators for clinical cardiac and brain studies, as well as other small field-of-view applications. This article reviews the basic principles of MPH collimators and introduces currently available and proposed clinical MPH SPECT systems

An improved nearest neighbor method for the estimation of the gamma photon entry point in monolithic scintillator detectors for PET

Several improvements of the k-nearest neighbor (k-NN) method for the determination of the entry point (x, y) of a gamma photon in a monolithic scintillator PET detector have been investigated with the aim to obtain better spatial resolution and/or to enable faster detector calibration by reducing the amount of required reference data and by allowing for calibrating with a line source. These methods were tested on a dataset measured with a SiPM-array-based monolithic LYSO detector. It appears that 10% to 25% better spatial resolution can be obtained compared to the standard approach. Moreover, some of the improved methods using two orders of magnitude less reference data, yield essentially the same spatial resolution as the standard method, which reduces the time needed for calibration as well as entry point computation. Finally, line source calibration is shown to be possible with some of the methods, yielding better results than the standard method and allowing much faster and easier collection of the reference data.</p

The role of preclinical SPECT in oncological and neurological research in combination with either CT or MRI

Preclinical imaging with SPECT combined with CT or MRI is used more and more frequently and has proven to be very useful in translational research. In this article, an overview of current preclinical research applications and trends of SPECT combined with CT or MRI, mainly in tumour imaging and neuroscience imaging, is given and the advan- tages and disadvantages of the different approaches are de- scribed. Today SPECT and CT systems are often integrated into a single device (commonly called a SPECT/CT system), whereas at present combined SPECT and MRI is almost always carried out with separate systems and fiducial markers to combine the separately acquired images. While preclinical SPECT/CT is most widely applied in oncology research, SPECT combined with MRI (SPECT/MRI when integrated in one system) offers the potential for both neuroscience applications and oncological applications. Today CT and MRI are still mainly used to localize radiotracer binding and to improve SPECT quantification, although both CT and MRI have additional potential. Future technology developments may include fast sequential or simultaneous acquisition of (dynamic) multimodality data, spectroscopy, fMRI along with high-resolution anatomic MRI, advanced CT procedures, and combinations of more than two modalities such as combina- tions of SPECT, PET, MRI and CT all together. This will all strongly depend on new technologies. With further advances in biology and chemistry for imaging molecular targets and (patho)physiological processes in vivo, the introduction of new imaging procedures and promising new radiopharmaceu- ticals in clinical practice may be accelerated

U-SPECT-BioFluo: an integrated radionuclide, bioluminescence, and fluorescence imaging platform

Background: In vivo bioluminescence, fluorescence, and single-photon emission computed tomography (SPECT) imaging provide complementary information about biological processes. However, to date these signatures are evaluated separately on individual preclinical systems. In this paper, we introduce a fully integrated bioluminescence-fluorescence-SPECT platform. Next to an optimization in logistics and image fusion, this integration can help improve understanding of the optical imaging (OI) results. Methods: An OI module was developed for a preclinical SPECT system (U-SPECT, MILabs, Utrecht, the Netherlands). The applicability of the module for bioluminescence and fluorescence imaging was evaluated in both a phantom and in an in vivo setting using mice implanted with a 4 T1-luc + tumor. A combination of a fluorescent dye and radioactive moiety was used to directly relate the optical images of the module to the SPECT findings. Bioluminescence imaging (BLI) was compared to the localization of the fluorescence signal in the tumors. Results: Both the phantom and in vivo mouse studies showed that superficial fluorescence signals could be imaged accurately. The SPECT and bioluminescence images could be used to place the fluorescence findings in perspective, e.g. by showing tracer accumulation in non-target organs such as the liver and kidneys (SPECT) and giving a semi-quantitative read-out for tumor spread (bioluminescence). Conclusions: We developed a fully integrated multimodal platform that provides complementary registered imaging of bioluminescent, fluorescent, and SPECT signatures in a single scanning session with a single dose of anesthesia. In our view, integration of these modalities helps to improve data interpretation of optical findings in relation to radionuclide images

Glymphatic-assisted perivascular brain delivery of intrathecal small gold nanoparticles

Nanoparticles are ultrafine particulate matter having considerable potential for treatment of central nervous system (CNS) disorders. Despite their tiny size, the blood-brain barrier (BBB) restricts their access to the CNS. Their direct cerebrospinal fluid (CSF) administration bypasses the BBB endothelium, but still fails to give adequate brain uptake. We present a novel approach for efficient CNS delivery of 111In-radiolabelled gold nanoparticles (AuNPs; 10-15 nm) via intra-cisterna magna administration, with tracking by SPECT imaging. To accelerate CSF brain influx, we administered AuNPs intracisternally in conjunction with systemic hypertonic saline, which dramatically increased the parenchymal AuNP uptake, especially in deep brain regions. AuNPs entered the CNS along periarterial spaces as visualized by MRI of gadolinium-labelled AuNPs and were cleared from brain within 24 h and excreted through the kidneys. Thus, the glymphatic-assisted perivascular network augment by systemic hypertonic saline is a pathway for highly efficient brain-wide distribution of small AuNPs.Peer reviewe

Influence of respiratory gating, image filtering, and animal positioning on high-resolution electrocardiography-gated murine cardiac single-photon emission computed tomography

Cardiac parameters obtained from single-photon emission computed tomographic (SPECT) images can be affected by respiratory motion, image filtering, and animal positioning. We investigated the influence of these factors on ultra-high-resolution murine myocardial perfusion SPECT. Five mice were injected with 99m technetium (99mTc)-tetrofosmin, and each was scanned in supine and prone positions in a U-SPECT-II scanner with respiratory and electrocardiographic (ECG) gating. ECG-gated SPECT images were created without applying respiratory motion correction or with two different respiratory motion correction strategies. The images were filtered with a range of three-dimensional gaussian kernels, after which end-diastolic volumes (EDVs), end-systolic volumes (ESVs), and left ventricular ejection fractions were calculated. No significant differences in the measured cardiac parameters were detected when any strategy to reduce or correct for respiratory motion was applied, whereas big differences (> 5%) in EDV and ESV were found with regard to different positioning of animals. A linear relationship (p < .001) was found between the EDV or ESV and the kernel size of the gaussian filter. In short, respiratory gating did not significantly affect the cardiac parameters of mice obtained with ultra-high-resolution SPECT, whereas the position of the animals and the image filters should be the same in a comparative study with multiple scans to avoid systematic differences in measured cardiac parameters

3D-printed saw guides for lower arm osteotomy, a comparison between a synthetic CT and CT-based workflow

BACKGROUND: Three-dimensional (3D)-printed saw guides are frequently used to optimize osteotomy results and are usually designed based on computed tomography (CT), despite the radiation burden, as radiation-less alternatives like magnetic resonance imaging (MRI) have inferior bone visualization capabilities. This study investigated the usability of MR-based synthetic-CT (sCT), a novel radiation-less bone visualization technique for 3D planning and design of patient-specific saw guides.METHODS: Eight human cadaveric lower arms (mean age: 78y) received MRI and CT scans as well as high-resolution micro-CT. From the MRI scans, sCT were generated using a conditional generative adversarial network. Digital 3D bone surface models based on the sCT and general CT were compared to the surface model from the micro-CT that was used as ground truth for image resolution. From both the sCT and CT digital bone models saw guides were designed and 3D-printed in nylon for one proximal and one distal bone position for each radius and ulna. Six blinded observers placed these saw guides as accurately as possible on dissected bones. The position of each guide was assessed by optical 3D-scanning of each bone with positioned saw guide and compared to the preplanning. Eight placement errors were evaluated: three translational errors (along each axis), three rotational errors (around each axis), a total translation (∆T) and a total rotation error (∆R).RESULTS: Surface models derived from micro-CT were on average smaller than sCT and CT-based models with average differences of 0.27 ± 0.30 mm for sCT and 0.24 ± 0.12 mm for CT. No statistically significant positioning differences on the bones were found between sCT- and CT-based saw guides for any axis specific translational or rotational errors nor between the ∆T (p = .284) and ∆R (p = .216). On Bland-Altman plots, the ∆T and ∆R limits of agreement (LoA) were within the inter-observer variability LoA.CONCLUSIONS: This research showed a similar error for sCT and CT digital surface models when comparing to ground truth micro-CT models. Additionally, the saw guide study showed equivalent CT- and sCT-based saw guide placement errors. Therefore, MRI-based synthetic CT is a promising radiation-less alternative to CT for the creation of patient-specific osteotomy surgical saw guides.</p

Absolute quantitative total-body small-animal SPECT with focusing pinholes

Purpose: In pinhole SPECT, attenuation of the photon flux on trajectories between source and pinholes affects quantitative accuracy of reconstructed images. Previously we introduced iterative methods that compensate for image degrading effects of detector and pinhole blurring, pinhole sensitivity and scatter for multi-pinhole SPECT. The aim of this paper is (1) to investigate the accuracy of the Chang algorithm in rodents and (2) to present a practical Changbased method using body outline contours obtained with optical cameras. Methods: Here we develop and experimentally validate a practical method for attenuation correction based on a Chang first-order method. This approach has the advantage that it is employed after, and therefore independently from, iterative reconstruction. Therefore, no new system matrix has to be calculated for each specific animal. Experiments with phantoms and animals were performed with a highresolution focusing multi-pinhole SPECT system (USPECT-II, MILabs, The Netherlands). This SPECT system provides three additional optical camera images of the animal for each SPECT scan from which the animal contour can be estimated. Results: Phantom experiments demonstrated that an average quantification error of –18.7% was reduced to –1.7% when both window-based scatter correction and Chang correction based on the body outline from optical images were applied. Without scatter and attenuation correction, quantification errors in a sacrificed rat containing sources with known activity ranged from –23.6 to –9.3%. These errors were reduced to values between –6.3 and +4.3% (with an average magnitude of 2.1%) after applying scatter and Chang attenuation correction. Conclusion: We conclude that the modified Chang correction based on body contour combined with window-based scatter correction is a practical method for obtaining small-animal SPECT images with high quantitative accuracy.Radiation, Radionuclides and ReactorsApplied Science

3D-printed saw guides for lower arm osteotomy, a comparison between a synthetic CT and CT-based workflow

BACKGROUND: Three-dimensional (3D)-printed saw guides are frequently used to optimize osteotomy results and are usually designed based on computed tomography (CT), despite the radiation burden, as radiation-less alternatives like magnetic resonance imaging (MRI) have inferior bone visualization capabilities. This study investigated the usability of MR-based synthetic-CT (sCT), a novel radiation-less bone visualization technique for 3D planning and design of patient-specific saw guides. METHODS: Eight human cadaveric lower arms (mean age: 78y) received MRI and CT scans as well as high-resolution micro-CT. From the MRI scans, sCT were generated using a conditional generative adversarial network. Digital 3D bone surface models based on the sCT and general CT were compared to the surface model from the micro-CT that was used as ground truth for image resolution. From both the sCT and CT digital bone models saw guides were designed and 3D-printed in nylon for one proximal and one distal bone position for each radius and ulna. Six blinded observers placed these saw guides as accurately as possible on dissected bones. The position of each guide was assessed by optical 3D-scanning of each bone with positioned saw guide and compared to the preplanning. Eight placement errors were evaluated: three translational errors (along each axis), three rotational errors (around each axis), a total translation (∆T) and a total rotation error (∆R). RESULTS: Surface models derived from micro-CT were on average smaller than sCT and CT-based models with average differences of 0.27 ± 0.30 mm for sCT and 0.24 ± 0.12 mm for CT. No statistically significant positioning differences on the bones were found between sCT- and CT-based saw guides for any axis specific translational or rotational errors nor between the ∆T (p = .284) and ∆R (p = .216). On Bland-Altman plots, the ∆T and ∆R limits of agreement (LoA) were within the inter-observer variability LoA. CONCLUSIONS: This research showed a similar error for sCT and CT digital surface models when comparing to ground truth micro-CT models. Additionally, the saw guide study showed equivalent CT- and sCT-based saw guide placement errors. Therefore, MRI-based synthetic CT is a promising radiation-less alternative to CT for the creation of patient-specific osteotomy surgical saw guides

Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach

Purpose: Atherosclerotic plaque development and progression signifies a complex inflammatory disease mediated by a multitude of proinflammatory leukocyte subsets. Using single photon emission computed tomography (SPECT) coupled with computed tomography (CT), this study tested a new dual-isotop