Walk-through flat panel total-body PET: a patient-centered design for high throughput imaging at lower cost using DOI-capable high-resolution monolithic detectors.

PURPOSE: Long axial field-of-view (LAFOV) systems have a much higher sensitivity than standard axial field-of-view (SAFOV) PET systems for imaging the torso or full body, which allows faster and/or lower dose imaging. Despite its very high sensitivity, current total-body PET (TB-PET) throughput is limited by patient handling (positioning on the bed) and often a shortage of available personnel. This factor, combined with high system costs, makes it hard to justify the implementation of these systems for many academic and nearly all routine nuclear medicine departments. We, therefore, propose a novel, cost-effective, dual flat panel TB-PET system for patients in upright standing positions to avoid the time-consuming positioning on a PET-CT table; the walk-through (WT) TB-PET. We describe a patient-centered, flat panel PET design that offers very efficient patient throughput and uses monolithic detectors (with BGO or LYSO) with depth-of-interaction (DOI) capabilities and high intrinsic spatial resolution. We compare system sensitivity, component costs, and patient throughput of the proposed WT-TB-PET to a SAFOV (= 26 cm) and a LAFOV (= 106 cm) LSO PET systems. METHODS: Patient width, height (= top head to start of thighs) and depth (= distance from the bed to front of patient) were derived from 40 randomly selected PET-CT scans to define the design dimensions of the WT-TB-PET. We compare this new PET system to the commercially available Siemens Biograph Vision 600 (SAFOV) and Siemens Quadra (LAFOV) PET-CT in terms of component costs, system sensitivity, and patient throughput. System cost comparison was based on estimating the cost of the two main components in the PET system (Silicon Photomultipliers (SiPMs) and scintillators). Sensitivity values were determined using Gate Monte Carlo simulations. Patient throughput times (including CT and scout scan, patient positioning on bed and transfer) were recorded for 1 day on a Siemens Vision 600 PET. These timing values were then used to estimate the expected patient throughput (assuming an equal patient radiotracer injected activity to patients and considering differences in system sensitivity and time-of-flight information) for WT-TB-PET, SAFOV and LAFOV PET. RESULTS: The WT-TB-PET is composed of two flat panels; each is 70 cm wide and 106 cm high, with a 50-cm gap between both panels. These design dimensions were justified by the patient sizes measured from the 40 random PET-CT scans. Each panel consists of 14 × 20 monolithic BGO detector blocks that are 50 × 50 × 16 mm in size and are coupled to a readout with 6 × 6 mm SiPMs arrays. For the WT-TB-PET, the detector surface is reduced by a factor of 1.9 and the scintillator volume by a factor of 2.2 compared to LAFOV PET systems, while demonstrating comparable sensitivity and much better uniform spatial resolution (< 2 mm in all directions over the FOV). The estimated component cost for the WT-TB-PET is 3.3 × lower than that of a 106 cm LAFOV system and only 20% higher than the PET component costs of a SAFOV. The estimated maximum number of patients scanned on a standard 8-h working day increases from 28 (for SAFOV) to 53-60 (for LAFOV in limited/full acceptance) to 87 (for the WT-TB-PET). By scanning faster (more patients), the amount of ordered activity per patient can be reduced drastically: the WT-TB-PET requires 66% less ordered activity per patient than a SAFOV. CONCLUSIONS: We propose a monolithic BGO or LYSO-based WT-TB-PET system with DOI measurements that departs from the classical patient positioning on a table and allows patients to stand upright between two flat panels. The WT-TB-PET system provides a solution to achieve a much lower cost TB-PET approaching the cost of a SAFOV system. High patient throughput is increased by fast patient positioning between two vertical flat panel detectors of high sensitivity. High spatial resolution (< 2 mm) uniform over the FOV is obtained by using DOI-capable monolithic scintillators.

The potential of a medium-cost long axial FOV PET system for nuclear medicine departments.

PURPOSE: Total body positron emission tomography (TB-PET) has recently been introduced in nuclear medicine departments. There is a large interest in these systems, but for many centers, the high acquisition cost makes it very difficult to justify their current operational budget. Here, we propose medium-cost long axial FOV scanners as an alternative. METHODS: Several medium-cost long axial FOV designs are described with their advantages and drawbacks. We describe their potential for higher throughput, more cost-effective scanning, a larger group of indications, and novel research opportunities. The wider spread of TB-PET can also lead to the fast introduction of new tracers (at a low dose), new methodologies, and optimized workflows. CONCLUSIONS: A medium-cost TB-PET would be positioned between the current standard PET-CT and the full TB-PET systems in investment but recapitulate most advantages of full TB-PET. These systems could be more easily justified financially in a standard academic or large private nuclear medicine department and still have ample research options.

18F-FDG micro-PET/CT for intra-operative margin assessment during breast-conserving surgery.

Rationale: Positive surgical margins for invasive breast cancer (BC) treated with breast-conserving surgery (BCS) are defined as ink on tumor. The rate of positive margins is approximately 20%, since a time- and cost-effective method for margin assessment is lacking. In this study, we investigated margin status by intra-operative imaging using high-resolution 18 F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) and X-ray computed tomography (CT).Methods: Twenty patients were enrolled and received 4 MBq/kg of FDG prior to surgery. Intra-operative imaging of the specimens was performed by the MOLECUBES ß-CUBE (PET) and X-CUBE (CT). Margin status was assessed by three surgeons and compared with an algorithm. The sensitivity and specificity were calculated by using histopathological assessment as a gold standard.Results: A region with high FDG uptake was visualized in all specimens. Automated analysis showed a sensitivity of 90%, a specificity of 60%, and an area under the curve (AUC) of 0.86 after ROC analysis. Margin assessment by the surgeons resulted in a mean sensitivity and specificity of 79% and 72%, respectively.Conclusions: This proof-of-concept study demonstrates that high-resolution FDG-PET/CT can facilitate intra-operative margin assessment during BCS. This technique achieves good sensitivity and specificity and may therefore reduce re-operation rates in the future.

Seizure Onset Zone Localization from Ictal High-Density EEG in Refractory Focal Epilepsy.

Epilepsy surgery is the most efficient treatment option for patients with refractory epilepsy. Before surgery, it is of utmost importance to accurately delineate the seizure onset zone (SOZ). Non-invasive EEG is the most used neuroimaging technique to diagnose epilepsy, but it is hard to localize the SOZ from EEG due to its low spatial resolution and because epilepsy is a network disease, with several brain regions becoming active during a seizure. In this work, we propose and validate an approach based on EEG source imaging (ESI) combined with functional connectivity analysis to overcome these problems. We considered both simulations and real data of patients. Ictal epochs of 204-channel EEG and subsets down to 32 channels were analyzed. ESI was done using realistic head models and LORETA was used as inverse technique. The connectivity pattern between the reconstructed sources was calculated, and the source with the highest number of outgoing connections was selected as SOZ. We compared this algorithm with a more straightforward approach, i.e. selecting the source with the highest power after ESI as the SOZ. We found that functional connectivity analysis estimated the SOZ consistently closer to the simulated EZ/RZ than localization based on maximal power. Performance, however, decreased when 128 electrodes or less were used, especially in the realistic data. The results show the added value of functional connectivity analysis for SOZ localization, when the EEG is obtained with a high-density setup. Next to this, the method can potentially be used as objective tool in clinical settings.

The Role of Skull Modeling in EEG Source Imaging for Patients with Refractory Temporal Lobe Epilepsy.

We investigated the influence of different skull modeling approaches on EEG source imaging (ESI), using data of six patients with refractory temporal lobe epilepsy who later underwent successful epilepsy surgery. Four realistic head models with different skull compartments, based on finite difference methods, were constructed for each patient: (i) Three models had skulls with compact and spongy bone compartments as well as air-filled cavities, segmented from either computed tomography (CT), magnetic resonance imaging (MRI) or a CT-template and (ii) one model included a MRI-based skull with a single compact bone compartment. In all patients we performed ESI of single and averaged spikes marked in the clinical 27-channel EEG by the epileptologist. To analyze at which time point the dipole estimations were closer to the resected zone, ESI was performed at two time instants: the half-rising phase and peak of the spike. The estimated sources for each model were validated against the resected area, as indicated by the postoperative MRI. Our results showed that single spike analysis was highly influenced by the signal-to-noise ratio (SNR), yielding estimations with smaller distances to the resected volume at the peak of the spike. Although averaging reduced the SNR effects, it did not always result in dipole estimations lying closer to the resection. The proposed skull modeling approaches did not lead to significant differences in the localization of the irritative zone from clinical EEG data with low spatial sampling density. Furthermore, we showed that a simple skull model (MRI-based) resulted in similar accuracy in dipole estimation compared to more complex head models (based on CT- or CT-template). Therefore, all the considered head models can be used in the presurgical evaluation of patients with temporal lobe epilepsy to localize the irritative zone from low-density clinical EEG recordings.

Fate of xylem-transported 11C- and 13C-labeled CO2 in leaves of poplar.

In recent studies, assimilation of xylem-transported CO2 has gained considerable attention as a means of recycling respired CO2 in trees. However, we still lack a clear and detailed picture on the magnitude of xylem-transported CO2 assimilation, in particular within leaf tissues. To this end, detached poplar leaves (Populus × canadensis Moench 'Robusta') were allowed to take up a dissolved (13)CO2 label serving as a proxy of xylem-transported CO2 entering the leaf from the branch. The uptake rate of the (13)C was manipulated by altering the vapor pressure deficit (VPD) (0.84, 1.29 and 1.83 kPa). Highest tissue enrichments were observed under the highest VPD. Among tissues, highest enrichment was observed in the petiole and the veins, regardless of the VPD treatment. Analysis of non-labeled leaves showed that some (13)C diffused from the labeled leaves and was fixed in the mesophyll of the non-labeled leaves. However, (13)C leaf tissue enrichment analysis with elemental analysis coupled to isotope ratio mass spectrometry was limited in spatial resolution at the leaf tissue level. Therefore, (11)C-based CO2 labeling combined with positron autoradiography was used and showed a more detailed spatial distribution within a single tissue, in particular in secondary veins. Therefore, in addition to (13)C, (11) C-based autoradiography can be used to study the fate of xylem-transported CO2 at leaf level, allowing the acquisition of data at a yet unprecedented resolution.

Bayesian model selection of template forward models for EEG source reconstruction.

Several EEG source reconstruction techniques have been proposed to identify the generating neuronal sources of electrical activity measured on the scalp. The solution of these techniques depends directly on the accuracy of the forward model that is inverted. Recently, a parametric empirical Bayesian (PEB) framework for distributed source reconstruction in EEG/MEG was introduced and implemented in the Statistical Parametric Mapping (SPM) software. The framework allows us to compare different forward modeling approaches, using real data, instead of using more traditional simulated data from an assumed true forward model. In the absence of a subject specific MR image, a 3-layered boundary element method (BEM) template head model is currently used including a scalp, skull and brain compartment. In this study, we introduced volumetric template head models based on the finite difference method (FDM). We constructed a FDM head model equivalent to the BEM model and an extended FDM model including CSF. These models were compared within the context of three different types of source priors related to the type of inversion used in the PEB framework: independent and identically distributed (IID) sources, equivalent to classical minimum norm approaches, coherence (COH) priors similar to methods such as LORETA, and multiple sparse priors (MSP). The resulting models were compared based on ERP data of 20 subjects using Bayesian model selection for group studies. The reconstructed activity was also compared with the findings of previous studies using functional magnetic resonance imaging. We found very strong evidence in favor of the extended FDM head model with CSF and assuming MSP. These results suggest that the use of realistic volumetric forward models can improve PEB EEG source reconstruction.

Multiple sparse volumetric priors for distributed EEG source reconstruction.

We revisit the multiple sparse priors (MSP) algorithm implemented in the statistical parametric mapping software (SPM) for distributed EEG source reconstruction (Friston et al., 2008). In the present implementation, multiple cortical patches are introduced as source priors based on a dipole source space restricted to a cortical surface mesh. In this note, we present a technique to construct volumetric cortical regions to introduce as source priors by restricting the dipole source space to a segmented gray matter layer and using a region growing approach. This extension allows to reconstruct brain structures besides the cortical surface and facilitates the use of more realistic volumetric head models including more layers, such as cerebrospinal fluid (CSF), compared to the standard 3-layered scalp-skull-brain head models. We illustrated the technique with ERP data and anatomical MR images in 12 subjects. Based on the segmented gray matter for each of the subjects, cortical regions were created and introduced as source priors for MSP-inversion assuming two types of head models. The standard 3-layered scalp-skull-brain head models and extended 4-layered head models including CSF. We compared these models with the current implementation by assessing the free energy corresponding with each of the reconstructions using Bayesian model selection for group studies. Strong evidence was found in favor of the volumetric MSP approach compared to the MSP approach based on cortical patches for both types of head models. Overall, the strongest evidence was found in favor of the volumetric MSP reconstructions based on the extended head models including CSF. These results were verified by comparing the reconstructed activity. The use of volumetric cortical regions as source priors is a useful complement to the present implementation as it allows to introduce more complex head models and volumetric source priors in future studies.

Use of a ray-based reconstruction algorithm to accurately quantify preclinical microSPECT images.

This work aimed to measure the in vivo quantification errors obtained when ray-based iterative reconstruction is used in micro-single-photon emission computed tomography (SPECT). This was investigated with an extensive phantom-based evaluation and two typical in vivo studies using 99mTc and 111In, measured on a commercially available cadmium zinc telluride (CZT)-based small-animal scanner. Iterative reconstruction was implemented on the GPU using ray tracing, including (1) scatter correction, (2) computed tomography-based attenuation correction, (3) resolution recovery, and (4) edge-preserving smoothing. It was validated using a National Electrical Manufacturers Association (NEMA) phantom. The in vivo quantification error was determined for two radiotracers: [99mTc]DMSA in naive mice (n  =  10 kidneys) and [111In]octreotide in mice (n  =  6) inoculated with a xenograft neuroendocrine tumor (NCI-H727). The measured energy resolution is 5.3% for 140.51 keV (99mTc), 4.8% for 171.30 keV, and 3.3% for 245.39 keV (111In). For 99mTc, an uncorrected quantification error of 28 ± 3% is reduced to 8 ± 3%. For 111In, the error reduces from 26 ± 14% to 6 ± 22%. The in vivo error obtained with 99mTc-dimercaptosuccinic acid ([99mTc]DMSA) is reduced from 16.2 ± 2.8% to -0.3 ± 2.1% and from 16.7 ± 10.1% to 2.2 ± 10.6% with [111In]octreotide. Absolute quantitative in vivo SPECT is possible without explicit system matrix measurements. An absolute in vivo quantification error smaller than 5% was achieved and exemplified for both [99mTc]DMSA and [111In]octreotide.

Influence of skull modeling approaches on EEG source localization.

Electroencephalographic source localization (ESL) relies on an accurate model representing the human head for the computation of the forward solution. In this head model, the skull is of utmost importance due to its complex geometry and low conductivity compared to the other tissues inside the head. We investigated the influence of using different skull modeling approaches on ESL. These approaches, consisting in skull conductivity and geometry modeling simplifications, make use of X-ray computed tomography (CT) and magnetic resonance (MR) images to generate seven different head models. A head model with an accurately segmented skull from CT images, including spongy and compact bone compartments as well as some air-filled cavities, was used as the reference model. EEG simulations were performed for a configuration of 32 and 128 electrodes, and for both noiseless and noisy data. The results show that skull geometry simplifications have a larger effect on ESL than those of the conductivity modeling. This suggests that accurate skull modeling is important in order to achieve reliable results for ESL that are useful in a clinical environment. We recommend the following guidelines to be taken into account for skull modeling in the generation of subject-specific head models: (i) If CT images are available, i.e., if the geometry of the skull and its different tissue types can be accurately segmented, the conductivity should be modeled as isotropic heterogeneous. The spongy bone might be segmented as an erosion of the compact bone; (ii) when only MR images are available, the skull base should be represented as accurately as possible and the conductivity can be modeled as isotropic heterogeneous, segmenting the spongy bone directly from the MR image; (iii) a large number of EEG electrodes should be used to obtain high spatial sampling, which reduces the localization errors at realistic noise levels.

Evaluation of lesion contrast in the walk-through long axial FOV PET scanner simulated with XCAT anthropomorphic phantoms.

BACKGROUND: This study evaluates the lesion contrast in a cost-effective long axial field of view (FOV) PET scanner, called the walk-through PET (WT-PET). The scanner consists of two flat detector panels covering the entire torso and head, scanning patients in an upright position for increased throughput. High-resolution, depth-of-interaction capable, monolithic detector technology is used to provide good spatial resolution and enable detection of smaller lesions. METHODS: Monte Carlo GATE simulations are used in conjunction with XCAT anthropomorphic phantoms to evaluate lesion contrast in lung, liver and breast for various lesion diameters (10, 7 and 5 mm), activity concentration ratios (8:1, 4:1 and 2:1) and patient BMIs (18-37). Images were reconstructed iteratively with listmode maximum likelihood expectation maximization, and contrast recovery coefficients (CRCs) were obtained for the reconstructed lesions. RESULTS: Results shows notable variations in contrast recovery coefficients (CRC) across different lesion sizes and organ locations within the XCAT phantoms. Specifically, our findings reveal that 10 mm lesions consistently exhibit higher CRC compared to 7 mm and 5 mm lesions, with increases of approximately 54% and 330%, respectively, across all investigated organs. Moreover, high contrast recovery is observed in most liver lesions regardless of diameter or activity ratio (average CRC = 42%), as well as in the 10 mm lesions in the lung. Notably, for the 10 mm lesions, the liver demonstrates 42% and 62% higher CRC compared to the lung and breast, respectively. This trend remains consistent across lesion sizes, with the liver consistently exhibiting higher CRC values compared to the lung and breast: 7 mm lesions show an increase of 96% and 41%, while 5 mm lesions exhibit approximately 294% and 302% higher CRC compared to the lung and breast, respectively. CONCLUSION: A comparison with a conventional pixelated LSO long axial FOV PET shows similar performance, achieved at a reduced cost for the WT-PET due to a reduction in required number of detectors.

Image Denoising of Low-Dose PET Mouse Scans with Deep Learning: Validation Study for Preclinical Imaging Applicability.

PURPOSE: Positron emission tomography (PET) image quality can be improved by higher injected activity and/or longer acquisition time, but both may often not be practical in preclinical imaging. Common preclinical radioactive doses (10 MBq) have been shown to cause deterministic changes in biological pathways. Reducing the injected tracer activity and/or shortening the scan time inevitably results in low-count acquisitions which poses a challenge because of the inherent noise introduction. We present an image-based deep learning (DL) framework for denoising lower count micro-PET images. PROCEDURES: For 36 mice, a 15-min [18F]FDG (8.15 ± 1.34 MBq) PET scan was acquired at 40 min post-injection on the Molecubes ß-CUBE (in list mode). The 15-min acquisition (high-count) was parsed into smaller time fractions of 7.50, 3.75, 1.50, and 0.75 min to emulate images reconstructed at 50, 25, 10, and 5% of the full counts, respectively. A 2D U-Net was trained with mean-squared-error loss on 28 high-low count image pairs. RESULTS: The DL algorithms were visually and quantitatively compared to spatial and edge-preserving denoising filters; the DL-based methods effectively removed image noise and recovered image details much better while keeping quantitative (SUV) accuracy. The largest improvement in image quality was seen in the images reconstructed with 10 and 5% of the counts (equivalent to sub-1 MBq or sub-1 min mouse imaging). The DL-based denoising framework was also successfully applied on the NEMA-NU4 phantom and different tracer studies ([18F]PSMA, [18F]FAPI, and [68 Ga]FAPI). CONCLUSION: Visual and quantitative results support the superior performance and robustness in image denoising of the implemented DL models for low statistics micro-PET. This offers much more flexibility in optimizing preclinical, longitudinal imaging protocols with reduced tracer doses or shorter durations.

Performance evaluation of small-animal multipinhole µSPECT scanners for mouse imaging.

PURPOSE: We compared the performance of three commercial small-animal µSPECT scanners equipped with multipinhole general purpose (GP) and multipinhole high-resolution (HR) collimators designed for imaging mice. METHODS: Spatial resolution, image uniformity, point source sensitivity and contrast recovery were determined for the U-SPECT-II (MILabs), the NanoSPECT-NSO (BioScan) and the X-SPECT (GE) scanners. The pinhole diameters of the HR collimator were 0.35 mm, 0.6 mm and 0.5 mm for these three systems respectively. A pinhole diameter of 1 mm was used for the GP collimator. To cover a broad field of imaging applications three isotopes were used with various photon energies: (99m)Tc (140 keV), (111)In (171 and 245 keV) and (125)I (27 keV). Spatial resolution and reconstructed image uniformity were evaluated in both HR and a GP mode with hot rod phantoms, line sources and a uniform phantom. Point source sensitivity and contrast recovery measures were additionally obtained in the GP mode with a novel contrast recovery phantom developed in-house containing hot and cold submillimetre capillaries on a warm background. RESULTS: In hot rod phantom images, capillaries as small as 0.4 mm with the U-SPECT-II, 0.75 mm with the X-SPECT and 0.6 mm with the NanoSPECT-NSO could be resolved with the HR collimators for (99m)Tc. The NanoSPECT-NSO achieved this resolution in a smaller field-of-view (FOV) and line source measurements showed that this device had a lower axial than transaxial resolution. For all systems, the degradation in image resolution was only minor when acquiring the more challenging isotopes (111)In and (125)I. The point source sensitivity with (99m)Tc and GP collimators was 3,984 cps/MBq for the U-SPECT-II, 620 cps/MBq for the X-SPECT and 751 cps/MBq for the NanoSPECT-NSO. The effects of volume sensitivity over a larger object were evaluated by measuring the contrast recovery phantom in a realistic FOV and acquisition time. For 1.5-mm rods at a noise level of 8 %, the contrast recovery coefficient (CRC) was 42 %, 37 % and 34 % for the U-SPECT-II, X-SPECT and NanoSPECT-NSO, respectively. At maximal noise levels of 10 %, a CRCcold of 70 %, 52 % and 42 % were obtained for the U-SPECT-II, X-SPECT and NanoSPECT-NSO, respectively. When acquiring (99m)Tc with the GP collimators, the integral/differential uniformity values were 30 %/14 % for the U-SPECT-II, 50 %/30 % for the X-SPECT and 38 %/25 % for the NanoSPECT-NSO. When using the HR collimators, these uniformity values remained similar for U-SPECT-II and X-SPECT, but not for the NanoSPECT-NSO for which the uniformity deteriorated with larger volumes. CONCLUSION: We compared three µSPECT systems by acquiring and analysing mouse-sized phantoms including a contrast recovery phantom built in-house offering the ability to measure the hot contrast on a warm background in the submillimetre resolution range. We believe our evaluation addressed the differences in imaging potential for each system to realistically image tracer distributions in mouse-sized objects.

Ictal-onset localization through connectivity analysis of intracranial EEG signals in patients with refractory epilepsy.

PURPOSE: Fifteen percent to 25% of patients with refractory epilepsy require invasive video-electroencephalography (EEG) monitoring (IVEM) to precisely delineate the ictal-onset zone. This delineation based on the recorded intracranial EEG (iEEG) signals occurs visually by the epileptologist and is therefore prone to human mistakes. The purpose of this study is to investigate whether effective connectivity analysis of intracranially recorded EEG during seizures provides an objective method to localize the ictal-onset zone. METHODS: In this study data were analyzed from eight patients who underwent IVEM at Ghent University Hospital in Belgium. All patients had a focal ictal onset and were seizure-free following resective surgery. The effective connectivity pattern was calculated during the first 20 s of ictal rhythmic iEEG activity. The out-degree, which is reflective of the number of outgoing connections, was calculated for each electrode contact for every single seizure during these 20 s. The seizure specific out-degrees were summed per patient to obtain the total out-degree. The electrode contact with the highest total out-degree was considered indicative of localization of the ictal-onset zone. This result was compared to the conclusion of the visual analysis of the epileptologist and the resected brain region segmented from postoperative magnetic resonance imaging (MRI). KEY FINDINGS: In all eight patients the electrode contact with the highest total out-degree was among the contacts identified by the epileptologist as the ictal onset. This contact, that we named "the driver," always laid within the resected brain region. Furthermore, the patient-specific connectivity patterns were consistent over the majority of seizures. SIGNIFICANCE: In this study we demonstrated the feasibility of correctly localizing the ictal-onset zone from iEEG recordings by using effective connectivity analysis during the first 20 s of ictal rhythmic iEEG activity.

Challenges and current methods for attenuation correction in PET/MR.

Quantitative PET imaging requires an attenuation map to correct for attenuation. In stand-alone PET or PET/CT, the attenuation map is usually derived from a transmission scan or CT image, respectively. In PET/MR, these methods will most likely not be used. Therefore, attenuation correction has long been regarded as one of the major challenges in the development of PET/MR. In the past few years, much progress has been made in this field. In this review, the challenges faced in attenuation correction for PET/MR are discussed. Different methods have been proposed to overcome these challenges. An overview of the MR-based (template-based and voxel-based), transmission-based and emission-based methods and the results that have been obtained is provided. Although several methods show promising results, no single method fulfils all of the requirements for the ideal attenuation correction method for PET/MR. Therefore, more work is still necessary in this field. To allow implementation in routine clinical practice, extensive evaluation of the proposed methods is necessary to demonstrate robustness and automation.

Effect of detector geometry and surface finish on Cerenkov based time estimation in monolithic BGO detectors.

Objective.Time-of-flight positron emission tomography based on bismuth germanate (BGO) detectors is made possible due to fast emission of Cerenkov light. Only around 17 Cerenkov photons are produced per 511 keV photoelectric event, making high photon collection efficiency crucial for obtaining good time-of-flight capabilities. In this study, we investigate how different lateral and back surface finishes affect the photon collection efficiency and Cerenkov based timing performance in monolithic BGO.Approach.The study is performed using GATE for gamma and optical photon modeling, with surface reflections of photons simulated by the LUT Davis model. We compare for different detector configurations (regarding size and surface finishes) the photon collection efficiency, detection delays of the first few optical photons and coincidence time resolution estimations obtained by modeling the SiPM signals and performing leading edge discrimination. An additional comparison is made to LYSO scintillators and pixelated detectors.Main results.Although Cerenkov photon emission is directional, many high incidence angle Cerenkov photons are emitted due to electron scattering in the crystal. Substituting a polished back (photodetector side) surface for a rough surface increases the collection efficiency of these high angle of incidence photons. Results show that for a monolithic 50 × 50 × 12 mm3BGO detector with reflective side surfaces, this leads to an overall increase in photon collection efficiency of 34%. Cerenkov photon collection efficiency is also improved, resulting in a reduction of the photon detection delays (and the variation therein) of the first few optical photons. This leads to a better coincidence time resolution, primarily achieved by a shortening of the tails in the time-of-flight kernel, with an 18% reduction in full width at tenth maximum.Significance.This study shows the importance of the photon collection efficiency for timing performance in Cerenkov based monolithic detectors, and how it can be improved with different surface finishes.

Dose reduction and image enhancement in micro-CT using deep learning.

BACKGROUND: In preclinical settings, micro-computed tomography (CT) provides a powerful tool to acquire high resolution anatomical images of rodents and offers the advantage to in vivo non-invasively assess disease progression and therapy efficacy. Much higher resolutions are needed to achieve scale-equivalent discriminatory capabilities in rodents as those in humans. High resolution imaging however comes at the expense of increased scan times and higher doses. Specifically, with preclinical longitudinal imaging, there are concerns that dose accumulation may affect experimental outcomes of animal models. PURPOSE: Dose reduction efforts under the ALARA (as low as reasonably achievable) principles are thus a key point of attention. However, low dose CT acquisitions inherently induce higher noise levels which deteriorate image quality and negatively impact diagnostic performance. Many denoising techniques already exist, and deep learning (DL) has become increasingly popular for image denoising, but research has mostly focused on clinical CT with limited studies conducted on preclinical CT imaging. We investigate the potential of convolutional neural networks (CNN) for restoring high quality micro-CT images from low dose (noisy) images. The novelty of the CNN denoising frameworks presented in this work consists of utilizing image pairs with realistic CT noise present in the input as well as the target image used for the model training; a noisier image acquired with a low dose protocol is matched to a less noisy image acquired with a higher dose scan of the same mouse. METHODS: Low and high dose ex vivo micro-CT scans of 38 mice were acquired. Two CNN models, based on a 2D and 3D four-layer U-Net, were trained with mean absolute error (30 training, 4 validation and 4 test sets). To assess denoising performance, ex vivo mice and phantom data were used. Both CNN approaches were compared to existing methods, like spatial filtering (Gaussian, Median, Wiener) and iterative total variation image reconstruction algorithm. Image quality metrics were derived from the phantom images. A first observer study (n = 23) was set-up to rank overall quality of differently denoised images. A second observer study (n = 18) estimated the dose reduction factor of the investigated 2D CNN method. RESULTS: Visual and quantitative results show that both CNN algorithms exhibit superior performance in terms of noise suppression, structural preservation and contrast enhancement over comparator methods. The quality scoring by 23 medical imaging experts also indicates that the investigated 2D CNN approach is consistently evaluated as the best performing denoising method. Results from the second observer study and quantitative measurements suggest that CNN-based denoising could offer a 2-4× dose reduction, with an estimated dose reduction factor of about 3.2 for the considered 2D network. CONCLUSIONS: Our results demonstrate the potential of DL in micro-CT for higher quality imaging at low dose acquisition settings. In the context of preclinical research, this offers promising future prospects for managing the cumulative severity effects of radiation in longitudinal studies.

Monte Carlo simulation of the system performance of a long axial field-of-view PET based on monolithic LYSO detectors.

BACKGROUND: In light of the milestones achieved in PET design so far, further sensitivity improvements aim to optimise factors such as the dose, throughput, and detection of small lesions. While several longer axial field-of-view (aFOV) PET systems based on pixelated detectors have been installed, continuous monolithic scintillation detectors recently gained increased attention due to their depth of interaction capability and superior intrinsic resolution. As a result, the aim of this work is to present and evaluate the performance of two long aFOV, monolithic LYSO-based PET scanner designs. METHODS: Geant4 Application for Tomographic Emission (GATE) v9.1 was used to perform the simulations. Scanner designs A and B have an aFOV of 36.2 cm (7 rings) and 72.6 cm (14 rings), respectively, with 40 detector modules per ring each and a bore diameter of 70 cm. Each module is a 50 × 50 × 16 mm3 monolithic LYSO crystal. Sensitivity, noise equivalent count rate (NECR), scatter fraction, spatial resolution, and image quality tests were performed based on NEMA NU-2018 standards. RESULTS: The sensitivity of design A was calculated to be 29.2 kcps/MBq at the centre and 27 kcps/MBq at 10 cm radial offset; similarly, the sensitivity of design B was found to be 106.8 kcps/MBq and 98.3 kcps/MBq at 10 cm radial offset. NECR peaks were reached at activity concentrations beyond the range of activities used for clinical studies. In terms of spatial resolution, the values for the point sources were below 2 mm for the radial, tangential, and axial full width half maximum. The contrast recovery coefficient ranged from 53% for design B and 4:1 contrast ratio to 90% for design A and 8:1 ratio, with a reasonably low background variability. CONCLUSIONS: Longer aFOV PET designs using monolithic LYSO have superior spatial resolution compared to current pixelated total-body PET (TB-PET) scanners. These systems combine high sensitivity with improved contrast recovery.