Direct co-registration of [18F]FDG uptake and histopathology in surgically excised malignancies of the head and neck: a feasibility study.

PURPOSE: Recent technical advancements in PET imaging have improved sensitivity and spatial resolution. Consequently, clinical nuclear medicine will be confronted with PET images on a previously unfamiliar resolution. To better understand [18F]FDG distribution at submillimetric scale, a direct correlation of radionuclide-imaging and histopathology is required. METHODS: A total of five patients diagnosed with a malignancy of the head and neck were injected with a clinical activity of [18F]FDG before undergoing surgical resection. The resected specimen was imaged using a preclinical high-resolution PET/CT, followed by slicing of the specimen. Multiple slices were rescanned using a micro-PET/CT device, and one of the slices was snap-frozen for frozen sections. Frozen sections were placed on an autoradiographic film, followed by haematoxylin and eosin staining to prepare them for histopathological assessment. The results from both autoradiography and histopathology were co-registered using an iterative co-registration algorithm, and regions of interest were identified to study radiotracer uptake. RESULTS: The co-registration between the autoradiographs and their corresponding histopathology was successful in all specimens. The use of this novel methodology allowed direct comparison of autoradiography and histopathology and enabled the visualisation of uncharted heterogeneity in [18F]FDG uptake in both benign and malignant tissue. CONCLUSION: We here describe a novel methodology enabling the direct co-registration of [18F]FDG autoradiography with the gold standard of histopathology in human malignant tissue. The future use of the current methodology could further increase our understanding of the distribution of radionuclides in surgically excised malignancies and hence, improve the integration of pathology and molecular imaging in a multiscale perspective. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05068687.

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.

A decision support system to follow up and diagnose primary headache patients using semantically enriched data.

BACKGROUND: Headache disorders are an important health burden, having a large health-economic impact worldwide. Current treatment & follow-up processes are often archaic, creating opportunities for computer-aided and decision support systems to increase their efficiency. Existing systems are mostly completely data-driven, and the underlying models are a black-box, deteriorating interpretability and transparency, which are key factors in order to be deployed in a clinical setting. METHODS: In this paper, a decision support system is proposed, composed of three components: (i) a cross-platform mobile application to capture the required data from patients to formulate a diagnosis, (ii) an automated diagnosis support module that generates an interpretable decision tree, based on data semantically annotated with expert knowledge, in order to support physicians in formulating the correct diagnosis and (iii) a web application such that the physician can efficiently interpret captured data and learned insights by means of visualizations. RESULTS: We show that decision tree induction techniques achieve competitive accuracy rates, compared to other black- and white-box techniques, on a publicly available dataset, referred to as migbase. Migbase contains aggregated information of headache attacks from 849 patients. Each sample is labeled with one of three possible primary headache disorders. We demonstrate that we are able to reduce the classification error, statistically significant (ρ≤0.05), with more than 10% by balancing the dataset using prior expert knowledge. Furthermore, we achieve high accuracy rates by using features extracted using the Weisfeiler-Lehman kernel, which is completely unsupervised. This makes it an ideal approach to solve a potential cold start problem. CONCLUSION: Decision trees are the perfect candidate for the automated diagnosis support module. They achieve predictive performances competitive to other techniques on the migbase dataset and are, foremost, completely interpretable. Moreover, the incorporation of prior knowledge increases both predictive performance as well as transparency of the resulting predictive model on the studied dataset.

A novel design for steerable instruments based on laser-cut nitinol.

OBJECTIVE: Omnidirectional articulated instruments enhance dexterity. In neurosurgery, for example, the simultaneous use of 2 instruments through the same endoscopic shaft remains a difficult feat. It is, however, very challenging to manufacture steerable instruments of the requisite small diameter. We present a new technique to produce such instruments by means of laser cutting. Only 3 coaxial tubes are used. The middle tube has a cutting pattern that allows the steering forces to be transmitted from the proximal to the distal end. In this way the steering part is concealed in the wall of the tube. Large diameter articulated instruments such as for laparoscopy might benefit from the excellent tip stability provided by the same economical technology. METHOD: Coaxial nitinol tubes are laser-cut with a Rofin Stent Cutter in a specific pattern. The 3 tubes are assembled by sliding them over one another, forming a single composite tube. In a surgical simulator, the neurosurgical microinstruments and laparoscopic needle drivers were evaluated on surgical convenience. RESULTS: Simultaneous use of 2 neurosurgical instruments (1.5 mm diameter) through the same endoscopic shaft proved to be very intuitive. The tip of the steerable laparoscopic instruments (10 mm diameter) could resist a lateral force of more than 20 N. The angle of motion for either instrument was at least 70° in any direction. CONCLUSIONS: A new design for steerable endoscopic instruments is presented. It allows the construction in a range from microinstruments to 10-mm laparoscopic devices with excellent tip stability.

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.

Magnetic resonace-based attenuation correction for micro-single-photon emission computed tomography.

Attenuation correction is necessary for quantification in micro-single-photon emission computed tomography (micro-SPECT). In general, this is done based on micro-computed tomographic (micro-CT) images. Derivation of the attenuation map from magnetic resonance (MR) images is difficult because bone and lung are invisible in conventional MR images and hence indistinguishable from air. An ultrashort echo time (UTE) sequence yields signal in bone and lungs. Micro-SPECT, micro-CT, and MR images of 18 rats were acquired. Different tracers were used: hexamethylpropyleneamine oxime (brain), dimercaptosuccinic acid (kidney), colloids (liver and spleen), and macroaggregated albumin (lung). The micro-SPECT images were reconstructed without attenuation correction, with micro-CT-based attenuation maps, and with three MR-based attenuation maps: uniform, non-UTE-MR based (air, soft tissue), and UTE-MR based (air, lung, soft tissue, bone). The average difference with the micro-CT-based reconstruction was calculated. The UTE-MR-based attenuation correction performed best, with average errors ≤ 8% in the brain scans and ≤ 3% in the body scans. It yields nonsignificant differences for the body scans. The uniform map yields errors of ≤ 6% in the body scans. No attenuation correction yields errors ≥ 15% in the brain scans and ≥ 25% in the body scans. Attenuation correction should always be performed for quantification. The feasibility of MR-based attenuation correction was shown. When accurate quantification is necessary, a UTE-MR-based attenuation correction should be used.

Automated ictal EEG source imaging: A retrospective, blinded clinical validation study.

OBJECTIVE: EEG source imaging (ESI) is a validated tool in the multimodal workup of patients with drug resistant focal epilepsy. However, it requires special expertise and it is underutilized. To circumvent this, automated analysis pipelines have been developed and validated for the interictal discharges. In this study, we present the clinical validation of an automated ESI for ictal EEG signals. METHODS: We have developed an automated analysis pipeline of ictal EEG activity, based on spectral analysis in source space, using an individual head model of six tissues. The analysis was done blinded to all other data. As reference standard, we used the concordance with the resected area and one-year postoperative outcome. RESULTS: We analyzed 50 consecutive patients undergoing epilepsy surgery (34 temporal and 16 extra-temporal). Thirty patients (60%) became seizure-free. The accuracy of the automated ESI was 74% (95% confidence interval: 59.66-85.37%). CONCLUSIONS: Automated ictal ESI has a high accuracy for localizing the seizure onset zone. SIGNIFICANCE: Automating the ESI of the ictal EEG signals will facilitate implementation of this tool in the presurgical evaluation.

The effect of errors in segmented attenuation maps on PET quantification.

PURPOSE: Accurate attenuation correction is important for PET quantification. Often, a segmented attenuation map is used, especially in MRI-based attenuation correction. As deriving the attenuation map from MRI images is difficult, different errors can be present in the segmented attenuation map. The goal of this paper is to determine the effect of these errors on quantification. METHODS: The authors simulated the digital XCAT phantom using the GATE Monte Carlo simulation framework and a model of the Philips Gemini TF. A whole body scan was simulated, spanning an axial field of view of 70 cm. A total of fifteen lesions were placed in the lung, liver, spine, colon, prostate, and femur. The acquired data were reconstructed with a reference attenuation map and with different attenuation maps that were modified to reflect common segmentation errors. The quantitative difference between reconstructed images was evaluated. RESULTS: Segmentation into five tissue classes, namely cortical bone, spongeous bone, soft tissue, lung, and air yielded errors below 5%. Large errors were caused by ignoring lung tissue (up to 45%) or cortical bone (up to 17%). The interpatient variability of lung attenuation coefficients can lead to errors of 10% and more. Up to 20% tissue misclassification from bone to soft tissue yielded errors below 5%. The same applies for up to 10% misclassification from lung to air. CONCLUSIONS: When using a segmented attenuation map, at least five different tissue types should be considered: cortical bone, spongeous bone, soft tissue, lung, and air. Furthermore, the interpatient variability of lung attenuation coefficients should be taken into account. Limited misclassification from bone to soft tissue and from lung to air is acceptable, as these do not lead to relevant errors.

High-Resolution 18F-FDG PET/CT for Assessing Three-Dimensional Intraoperative Margins Status in Malignancies of the Head and Neck, a Proof-of-Concept.

The surgical treatment of head and neck malignancies relies on the complete removal of tumoral tissue, while inadequate margins necessitate the use of adjuvant therapy. However, most positive margins are identified postoperatively as deep margins, and intraoperative identification of the deep positive margins could help achieve adequate surgical margins and decrease adjuvant therapies. To improve deep-margin identification, we investigated whether the use of high-resolution preclinical PET and CT could increase certainty about the surgical margins in three dimensions. Patients with a malignancy of the head and neck planned for surgical resection were administered a clinical activity of 4MBq/kg 18F-FDG approximately one hour prior to surgical initiation. Subsequently, the resected specimen was scanned with a micro-PET-CT imaging device, followed by histopathological assessment. Eight patients were included in the study and intraoperative PET/CT-imaging of 11 tumoral specimens and lymph nodes of three patients was performed. As a result of the increased resolution, differentiation between inflamed and dysplastic tissue versus malignant tissue was complicated in malignancies with increased peritumoral inflammation. The current technique allowed the three-dimensional delineation of 18F-FDG using submillimetric PET/CT imaging. While further optimization and patient stratification is required, clinical implementation could enable deep margin assessment in head and neck resection specimens.

Wall-eyed Bilateral Internuclear Ophthalmoplegia (WEBINO) in a Patient With Idiopathic Intracranial Hypertension.

INTRODUCTION: Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is a variant syndrome of internuclear ophthalmoplegia, consisting of primary gaze exotropia, adduction impairment, nystagmus of the abducting eye, and vertical gaze-evoked nystagmus. It seems to be most frequently associated with multiple sclerosis, although other etiologies such as brainstem ischemia or hydrocephalus have also been described. CASE REPORT: We report the case of a 25-year-old woman who presented with subacute progressive oculomotor disturbances, resulting in the development of a WEBINO over a few days. Fundoscopy showed papilledema first in the right and afterwards also in the left eye. Brain magnetic resonance imaging was normal. Lumbar puncture demonstrated an opening pressure of 38 cm H2O, without pleiocytosis and with normal protein. As no other cause of intracranial hypertension could be identified by imaging or extensive biochemical testing, the patient was treated with acetazolamide for idiopathic intracranial hypertension. As there was further progression despite increase of acetazolamide dosing, more aggressive therapy was pursued, and a ventriculoperitoneal shunt was placed by our neurosurgeons. Clinical follow-up showed progressive recovery of normal oculomotor function and disappearance of papilledema over the course of 6 weeks. CONCLUSIONS: To our knowledge this is the first case description of a patient with WEBINO and idiopathic intracranial hypertension. The diagnosis is supported by the very high opening pressure, the absence of neuroimaging abnormalities, the papilledema, and the response to ventriculoperitoneal drainage.

Automated long-term EEG analysis to localize the epileptogenic zone.

Objective: We investigated the performance of automatic spike detection and subsequent electroencephalogram (EEG) source imaging to localize the epileptogenic zone (EZ) from long-term EEG recorded during video-EEG monitoring. Methods: In 32 patients, spikes were automatically detected in the EEG and clustered according to their morphology. The two spike clusters with most single events in each patient were averaged and localized in the brain at the half-rising time and peak of the spike using EEG source imaging. On the basis of the distance from the sources to the resection and the known patient outcome after surgery, the performance of the automated EEG analysis to localize the EZ was quantified. Results: In 28 out of the 32 patients, the automatically detected spike clusters corresponded with the reported interictal findings. The median distance to the resection in patients with Engel class I outcome was 6.5 and 15 mm for spike cluster 1 and 27 and 26 mm for cluster 2, at the peak and the half-rising time of the spike, respectively. Spike occurrence (cluster 1 vs. cluster 2) and spike timing (peak vs. half-rising) significantly influenced the distance to the resection (p < 0.05). For patients with Engel class II, III, and IV outcomes, the median distance increased to 36 and 36 mm for cluster 1. Localizing spike cluster 1 at the peak resulted in a sensitivity of 70% and specificity of 100%, positive prediction value (PPV) of 100%, and negative predictive value (NPV) of 53%. Including the results of spike cluster 2 led to an increased sensitivity of 79% NPV of 55% and diagnostic OR of 11.4, while the specificity dropped to 75% and the PPV to 90%. Significance: We showed that automated analysis of long-term EEG recordings results in a high sensitivity and specificity to localize the epileptogenic focus.

EEG source connectivity to localize the seizure onset zone in patients with drug resistant epilepsy.

Electrical source imaging (ESI) from interictal scalp EEG is increasingly validated and used as a valuable tool in the presurgical evaluation of epilepsy as a reflection of the irritative zone. ESI of ictal scalp EEG to localize the seizure onset zone (SOZ) remains challenging. We investigated the value of an approach for ictal imaging using ESI and functional connectivity analysis (FC). Ictal scalp EEG from 111 seizures in 27 patients who had Engel class I outcome at least 1 year following resective surgery was analyzed. For every seizure, an artifact-free epoch close to the seizure onset was selected and ESI using LORETA was applied. In addition, the reconstructed sources underwent FC using the spectrum-weighted Adaptive Directed Transfer Function. This resulted in the estimation of the SOZ in two ways: (i) the source with maximal power after ESI, (ii) the source with the strongest outgoing connections after combined ESI and FC. Next, we calculated the distance between the estimated SOZ and the border of the resected zone (RZ) for both approaches and called this the localization error ((i) LEpow and (ii) LEconn respectively). By comparing LEpow and LEconn, we assessed the added value of FC. The source with maximal power after ESI was inside the RZ (LEpow = 0 mm) in 31% of the seizures and estimated within 10 mm from the border of the RZ (LEpow ≤ 10 mm) in 42%. Using ESI and FC, these numbers increased to 72% for LEconn = 0 mm and 94% for LEconn ≤ 10 mm. FC provided a significant added value to ESI alone (p < 0.001). ESI combined with subsequent FC is able to localize the SOZ in a non-invasive way with high accuracy. Therefore it could be a valuable tool in the presurgical evaluation of epilepsy.

Hippocampal deep brain stimulation reduces glucose utilization in the healthy rat brain.

PURPOSE: The effects of deep brain stimulation (DBS) have been studied primarily by cellular studies, which lack the ability to elucidate DBS-related responses on a whole-brain scale. 2-Deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography ([(18)F]FDG-PET) reflects changes in neural activity throughout the entire brain volume. The aim of this study was to investigate the whole-brain effect of DBS on the glucose utilization in healthy rats. PROCEDURES: Seven rats were implanted with a DBS electrode in the right hippocampus and injected with [(18)F]FDG to measure the glucose metabolism during DBS. RESULTS: Analysis reveals significant DBS-induced decreases in the glucose metabolism in the bilateral hippocampus and other limbic structures. CONCLUSIONS: This study demonstrates that DBS exhibits not only a local effect around the electrode tip but also in other limbic regions. [(18)F]FDG-PET studies have the potential to provide better insight into the mechanism of action of DBS by simultaneously observing activity at multiple sites in the brain.

Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain.

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS.

DigiPET: sub-millimeter spatial resolution small-animal PET imaging using thin monolithic scintillators.

A new preclinical PET system based on dSiPMs, called DigiPET, is presented. The system is based on thin monolithic scintillation crystals and exhibits superior spatial resolution at low-cost compared to systems based on pixelated crystals. Current dedicated small-rodent PET scanners have a spatial resolution in the order of 1 mm. Most of them have a large footprint, requiring considerable laboratory space. For rodent brain imaging, a PET scanner with sub-millimeter resolution is desired. To achieve this, crystals with a pixel pitch down to 0.5 mm have been used. However, fine pixels are difficult to produce and will render systems expensive. In this work, we present the first results with a high-resolution preclinical PET scanner based on thin monolithic scintillators and a large solid angle. The design is dedicated to rat-brain imaging and therefore has a very compact geometry. Four detectors were placed in a square arrangement with a distance of 34.5 mm between two opposing detector modules, defining a field of view (FOV) of 32 × 32 × 32 mm(3). Each detector consists of a thin monolithic LYSO crystal of 32 × 32 × 2 mm(3) optically coupled to a digital silicon photomultiplier (dSiPM). Event positioning within each detector was obtained using the maximum likelihood estimation (MLE) method. To evaluate the system performance, we measured the energy resolution, coincidence resolving time (CRT), sensitivity and spatial resolution. The image quality was evaluated by acquiring a hot-rod phantom filled with (18)F-FDG and a rat head one hour after an (18)F-FDG injection. The MLE yielded an average intrinsic spatial resolution on the detector of 0.54 mm FWHM. We obtained a CRT of 680 ps and an energy resolution of 18% FWHM at 511 keV. The sensitivity and spatial resolution obtained at the center of the FOV were 6.0 cps kBq(-1) and 0.7 mm, respectively. In the reconstructed images of the hot-rod phantom, hot rods down to 0.7 mm can be discriminated. In conclusion, a compact PET scanner was built using dSiPM technology and thin monolithic LYSO crystals. Excellent spatial resolution and acceptable sensitivity were demonstrated. Promising results were also obtained in a hot-rod phantom and in rat-brain imaging.

Improvement of attenuation correction in time-of-flight PET/MR imaging with a positron-emitting source.

UNLABELLED: Quantitative PET imaging relies on accurate attenuation correction. Recently, there has been growing interest in combining state-of-the-art PET systems with MR imaging in a sequential or fully integrated setup. As CT becomes unavailable for these systems, an alternative approach to the CT-based reconstruction of attenuation coefficients (µ values) at 511 keV must be found. Deriving µ values directly from MR images is difficult because MR signals are related to the proton density and relaxation properties of tissue. Therefore, most research groups focus on segmentation or atlas registration techniques. Although studies have shown that these methods provide viable solutions in particular applications, some major drawbacks limit their use in whole-body PET/MR. Previously, we used an annulus-shaped PET transmission source inside the field of view of a PET scanner to measure attenuation coefficients at 511 keV. In this work, we describe the use of this method in studies of patients with the sequential time-of-flight (TOF) PET/MR scanner installed at the Icahn School of Medicine at Mount Sinai, New York, NY. METHODS: Five human PET/MR and CT datasets were acquired. The transmission-based attenuation correction method was compared with conventional CT-based attenuation correction and the 3-segment, MR-based attenuation correction available on the TOF PET/MR imaging scanner. RESULTS: The transmission-based method overcame most problems related to the MR-based technique, such as truncation artifacts of the arms, segmentation artifacts in the lungs, and imaging of cortical bone. Additionally, the TOF capabilities of the PET detectors allowed the simultaneous acquisition of transmission and emission data. Compared with the MR-based approach, the transmission-based method provided average improvements in PET quantification of 6.4%, 2.4%, and 18.7% in volumes of interest inside the lung, soft tissue, and bone tissue, respectively. CONCLUSION: In conclusion, a transmission-based technique with an annulus-shaped transmission source will be more accurate than a conventional MR-based technique for measuring attenuation coefficients at 511 keV in future whole-body PET/MR studies.

Temperature dependence of APD-based PET scanners.

PURPOSE: Solid state detectors such as avalanche photodiodes (APDs) are increasingly being used in PET detectors. One of the disadvantages of APDs is the strong decrease of their gain factor with increasing ambient temperature. The light yield of most scintillation crystals also decreases when ambient temperature is increased. Both effects lead to considerable temperature dependence of the performance of APD-based PET scanners. In this paper, the authors propose a model for this dependence and the performance of the LabPET8 APD-based small animal PET scanner is evaluated at different temperatures. METHODS: The model proposes that the effect of increasing temperature on the energy histogram of an APD-based PET scanner is a compression of the histogram along the energy axis. The energy histogram of the LabPET system was acquired at 21 °C and 25 °C to verify the validity of this model. Using the proposed model, the effect of temperature on system sensitivity was simulated for different detector temperature coefficients and temperatures. Subsequently, the effect of short term and long term temperature changes on the peak sensitivity of the LabPET system was measured. The axial sensitivity profile was measured at 21 °C and 24 °C following the NEMA NU 4-2008 standard. System spatial resolution was also evaluated. Furthermore, scatter fraction, count losses and random coincidences were evaluated at different temperatures. Image quality was also investigated. RESULTS: As predicted by the model, the photopeak energy at 25 °C is lower than at 21 °C with a shift of approximately 6% per °C. Simulations showed that this results in an approximately linear decrease of sensitivity when temperature is increased from 21 °C to 24 °C and energy thresholds are constant. Experimental evaluation of the peak sensitivity at different temperatures showed a strong linear correlation for short term (2.32 kcps/MBq/°C = 12%/°C, R = -0.95) and long term (1.92 kcps/MBq/°C = 10%/°C , R = -0.96) temperature changes. Count rate evaluation showed that although the total count rate is consistently higher at 21 °C than at 24 °C for different source activity concentrations, this is mainly due to an increase in scattered and random coincidences. The peak total count rate is 400 kcps at both temperatures but is reached at lower activity at 21 °C. The peak true count rate is 138 kcps (at 100 MBq) at 21 °C and 180 kcps (at 125 MBq) at 24 °C. The peak noise equivalent count rate is also lower at 21 °C (70 kcps at 70 MBq) than at 24 °C (100 kcps at 100 MBq). At realistic activity levels, the scatter fraction is lower at higher temperatures, but at the cost of a strong decrease in true count rate. CONCLUSIONS: A model was proposed for the temperature dependence of APD-based PET scanners and evaluated using the LabPET small animal PET scanner. System sensitivity and count rate performance are strongly dependent on ambient temperature while system resolution is not. The authors' results indicate that it is important to assure stable ambient temperature to obtain reproducible results in imaging studies with APD-based PET scanners.

Influence of detector pixel size, TOF resolution and DOI on image quality in MR-compatible whole-body PET.

The optimization of a whole-body PET system remains a challenging task, as the imaging performance is influenced by a complex interaction of different design parameters. However, it is not always clear which parameters have the largest impact on image quality and are most eligible for optimization. To determine this, we need to be able to assess their influence on image quality. We performed Monte-Carlo simulations of a whole-body PET scanner to predict the influence on image quality of three detector parameters: the TOF resolution, the transverse pixel size and depth-of-interaction (DOI)-correction. The inner diameter of the PET scanner was 65 cm, small enough to allow physical integration into a simultaneous PET-MR system. Point sources were used to evaluate the influence of transverse pixel size and DOI-correction on spatial resolution as function of radial distance. To evaluate the influence on contrast recovery and pixel noise a cylindrical phantom of 35 cm diameter was used, representing a large patient. The phantom contained multiple hot lesions with 5 mm diameter. These lesions were placed at radial distances of 50, 100 and 150 mm from the center of the field-of-view, to be able to study the effects at different radial positions. The non-prewhitening (NPW) observer was used for objective analysis of the detectability of the hot lesions in the cylindrical phantom. Based on this analysis the NPW-SNR was used to quantify the relative improvements in image quality due to changes of the variable detector parameters. The image quality of a whole-body PET scanner can be improved significantly by reducing the transverse pixel size from 4 to 2.6 mm and improving the TOF resolution from 600 to 400 ps and further from 400 to 200 ps. Compared to pixel size, the TOF resolution has the larger potential to increase image quality for the simulated phantom. The introduction of two layer DOI-correction only leads to a modest improvement for the spheres at radial distance of 150 mm from the center of the transaxial FOV.

Simultaneous MR-compatible emission and transmission imaging for PET using time-of-flight information.

Quantitative positron emission tomography (PET) imaging relies on accurate attenuation correction. Predicting attenuation values from magnetic resonance (MR) images is difficult because MR signals are related to proton density and relaxation properties of tissues. Here, we propose a method to derive the attenuation map from a transmission scan. An annulus transmission source is positioned inside the field-of-view of the PET scanner. First a blank scan is acquired. The patient is injected with FDG and placed inside the scanner. 511-keV photons coming from the patient and the transmission source are acquired simultaneously. Time-of-flight information is used to extract the coincident photons originating from the annulus. The blank and transmission data are compared in an iterative reconstruction method to derive the attenuation map. Simulations with a digital phantom were performed to validate the method. The reconstructed attenuation coefficients differ less than 5% in volumes of interest inside the lungs, bone, and soft tissue. When applying attenuation correction in the reconstruction of the emission data a standardized uptake value error smaller than 9% was obtained for all tissues. In conclusion, our method can reconstruct the attenuation map and the emission data from a simultaneous scan without prior knowledge about the anatomy or the attenuation coefficients of the tissues.