Resolution enhancement, noise suppression, and joint T2* decay estimation in dual-echo sodium-23 MR imaging using anatomically guided reconstruction.

PURPOSE: Sodium MRI is challenging because of the low tissue concentration of the 23 Na nucleus and its extremely fast biexponential transverse relaxation rate. In this article, we present an iterative reconstruction framework using dual-echo 23 Na data and exploiting anatomical prior information (AGR) from high-resolution, low-noise, 1 H MR images. This framework enables the estimation and modeling of the spatially varying signal decay due to transverse relaxation during readout (AGRdm), which leads to images of better resolution and reduced noise resulting in improved quantification of the reconstructed 23 Na images. METHODS: The proposed framework was evaluated using reconstructions of 30 noise realizations of realistic simulations of dual echo twisted projection imaging (TPI) 23 Na data. Moreover, three dual echo 23 Na TPI brain datasets of healthy controls acquired on a 3T Siemens Prisma system were reconstructed using conventional reconstruction, AGR and AGRdm. RESULTS: Our simulations show that compared to conventional reconstructions, AGR and AGRdm show improved bias-noise characteristics in several regions of the brain. Moreover, AGR and AGRdm images show more anatomical detail and less noise in the reconstructions of the experimental data sets. Compared to AGR and the conventional reconstruction, AGRdm shows higher contrast in the sodium concentration ratio between gray and white matter and between gray matter and the brain stem. CONCLUSION: AGR and AGRdm generate 23 Na images with high resolution, high levels of anatomical detail, and low levels of noise, potentially enabling high-quality 23 Na MR imaging at 3T.

Approximating anatomically-guided PET reconstruction in image space using a convolutional neural network.

In the last two decades, it has been shown that anatomically-guided PET reconstruction can lead to improved bias-noise characteristics in brain PET imaging. However, despite promising results in simulations and first studies, anatomically-guided PET reconstructions are not yet available for use in routine clinical because of several reasons. In light of this, we investigate whether the improvements of anatomically-guided PET reconstruction methods can be achieved entirely in the image domain with a convolutional neural network (CNN). An entirely image-based CNN post-reconstruction approach has the advantage that no access to PET raw data is needed and, moreover, that the prediction times of trained CNNs are extremely fast on state of the art GPUs which will substantially facilitate the evaluation, fine-tuning and application of anatomically-guided PET reconstruction in real-world clinical settings. In this work, we demonstrate that anatomically-guided PET reconstruction using the asymmetric Bowsher prior can be well-approximated by a purely shift-invariant convolutional neural network in image space allowing the generation of anatomically-guided PET images in almost real-time. We show that by applying dedicated data augmentation techniques in the training phase, in which 16 [18F]FDG and 10 [18F]PE2I data sets were used, lead to a CNN that is robust against the used PET tracer, the noise level of the input PET images and the input MRI contrast. A detailed analysis of our CNN in 36 [18F]FDG, 18 [18F]PE2I, and 7 [18F]FET test data sets demonstrates that the image quality of our trained CNN is very close to the one of the target reconstructions in terms of regional mean recovery and regional structural similarity.

Left ventricular regional glucose metabolism in combination with septal scar extent identifies CRT responders.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in selective heart failure (HF) patients, but non-response rate remains high. Positron emission tomography (PET) may provide a better insight into the pathophysiology of left ventricular (LV) remodeling; however, its role for evaluating and selecting patients for CRT remains uncertain. PURPOSE: We investigated if regional LV glucose metabolism in combination with myocardial scar could predict response to CRT. METHODS: Consecutive CRT-eligible HF patients underwent echocardiography, cardiac magnetic resonance (CMR), and 18F-fluorodeoxyglucose (FDG) PET within 1 week before CRT implantation. Echocardiography was additionally performed 12 months after CRT and end-systolic volume reduction ≥ 15% was defined as CRT response. Septal-to-lateral wall (SLR) FDG uptake ratio was calculated from static FDG images. Late gadolinium enhancement (LGE) CMR was analyzed semi-quantitatively to define scar extent. RESULTS: We evaluated 88 patients (67 ± 10 years, 72% males). 18F-FDG SLR showed a linear correlation with volumetric reverse remodeling 12 months after CRT (r = 0.41, p = 0.0001). In non-ischemic HF patients, low FDG SLR alone predicted CRT response with sensitivity and specificity of more than 80%; however, in ischemic HF patients, specificity decreased to 46%, suggesting that in this cohort low SLR can also be caused by the presence of a septal scar. In the multivariate logistic regression model, including low FDG SLR, presence and extent of the scar in each myocardial wall, and current CRT guideline parameters, only low FDG SLR and septal scar remained associated with CRT response. Their combination could predict CRT response with sensitivity, specificity, negative, and positive predictive value of 80%, 83%, 70%, and 90%, respectively. CONCLUSIONS: FDG SLR can be used as a predictor of CRT response and combined with septal scar extent, CRT responders can be distinguished from non-responders with high diagnostic accuracy. Further studies are needed to verify whether this imaging approach can prospectively be used to optimize patient selection.

Impact of left bundle branch block on myocardial perfusion and metabolism: A positron emission tomography study.

BACKGROUND: Better understanding of pathophysiological changes, induced by left bundle branch block (LBBB), may improve patient selection for cardiac resynchronization therapy (CRT). Therefore, we assessed the effect of LBBB on regional glucose metabolism, 13N-NH3-derived absolute and semiquantitative myocardial blood flow (MBF), and their relation in non-ischemic CRT candidates. METHODS: Twenty-five consecutive non-ischemic patients with LBBB underwent 18F-FDG and resting dynamic 13N-NH3 PET/CT prior to CRT implantation. Regional 18F-FDG uptake, absolute MBF, and late 13N-NH3 uptake were analyzed and corresponding septal-to-lateral wall ratios (SLR) were calculated. Segmental analysis was performed to evaluate "reverse mismatch," "mismatch," and "match" patterns, based on late 13N-NH3/18F-FDG uptake ratios. RESULTS: A significantly lower 18F-FDG uptake was observed in the septum compared to the lateral wall (SLR 0.53 ± 0.17). A similar pattern was observed for MBF (SLR 0.68 ± 0.18), whereas late 13N-NH3 uptake showed a homogeneous distribution (SLR 0.96 ± 0.13). 13N-NH3/18F-FDG "mismatch" and "reverse mismatch" segments were predominantly present in the lateral (52%) and septal wall (61%), respectively. CONCLUSIONS: Non-ischemic CRT candidates with LBBB demonstrate lower glucose uptake and absolute MBF in the septum compared to the lateral wall. However, late static 13N-NH3 uptake showed a homogenous distribution, reflecting a composite measure of altered regional MBF and metabolism, induced by LBBB.

Gamma Camera Imaging with Rotating Multi-Pinhole Collimator. A Monte Carlo Feasibility Study.

In this work, we propose and analyze a new concept of gamma ray imaging that corresponds to a gamma camera with a mobile collimator, which can be used in vivo, during surgical interventions for oncological patients for localizing regions of interest such as tumors or ganglia. The benefits are a much higher sensitivity, better image quality and, consequently, a dose reduction for the patient and medical staff. This novel approach is a practical solution to the overlapping problem which is inherent to multi-pinhole gamma camera imaging and single photon emission computed tomography and which translates into artifacts and/or image truncation in the final reconstructed image. The key concept consists in introducing a relative motion between the collimator and the detector. Moreover, this design could also be incorporated into most commercially available gamma camera devices, without any excessive additional requirements. We use Monte Carlo simulations to assess the feasibility of such a device, analyze three possible designs and compare their sensitivity, resolution and uniformity. We propose a final design of a gamma camera with a high sensitivity ranging from 0.001 to 0.006 cps/Bq, and a high resolution of 0.5-1.0 cm (FWHM), for source-to-detector distances of 4-10 cm. Additionally, this planar gamma camera provides information about the depth of source (with approximate resolution of 1.5 cm) and excellent image uniformity.

Quantification and discriminative power of 18F-FE-PE2I PET in patients with Parkinson's disease.

RATIONALE: Dopamine transporter (DAT) imaging is an important adjunct in the diagnostic workup of patients with Parkinsonism. 18F-FE-PE2I is a suitable PET radioligand for DAT quantification and imaging with good pharmacokinetics. The aim of this study was to determine a clinical optimal simplified reference tissue-based image acquisition protocol and to compare the discriminatory value and effect size for 18F-FE-PE2I to that for 123I-FP-CIT scan currently used in clinical practice. METHODS: Nine patients with early Parkinson's disease (PD, 64.3 ± 6.8 years, 3M), who had previously undergone a 123I-FP-CIT scan as part of their diagnostic workup, and 34 healthy volunteers (HV, 47.7 ± 16.8 years, 13M) underwent a 60-min dynamic 18F-FE-PE2I PET-MR scan on a GE Signa 3T PET-MR. Based on dynamic data and MR-based VOI delineation, BPND, semi-quantitative uptake ratio and SUVR[t1-t2] images were calculated using either occipital cortex or cerebellum as reference region. For start-and-end time of the SUVR interval, three time frames [t1-t2] were investigated: [15-40] min, [40-60] min, and [50-60] min postinjection. Data for putamen (PUT) and caudate nucleus-putamen ratio (CPR) were compared in terms of quantification bias versus BPND and discriminative power. RESULTS: Using occipital cortex as reference region resulted in smaller bias of SUVR with respect to BPND + 1 and higher correlation between SUVR and BPND + 1 compared with using cerebellum, irrespective of SUVR [t1-t2] interval. Smallest bias was observed with the [15-40]-min time window, in accordance with previous literature. The correlation between BPND + 1 and SUVR was slightly better for the late time windows. Discriminant analysis between PD and HV using both PUT and CPR SUVRs showed an accuracy of ≥ 90%, for both reference regions and all studied time windows. Semi-quantitative 123I-FP-CIT and 18F-FE-PE2I values and relative decrease in the striatum for patients were highly correlated, with a higher effect size for 18F-FE-PE2I for PUT and CPR SUVR. CONCLUSION: 18F-FE-PE2I is a suitable radioligand for in vivo DAT imaging with high discriminative power between early PD and healthy controls. Whereas a [15-40]-min window has lowest bias with respect to BPND, a [50-60]-min time window at pseudoequilibrium can be advocated in terms of clinical feasibility with optimal discriminative power. The occipital cortex may be slightly preferable as reference region because of the higher time stability, stronger correlation of SUVR with BPND + 1, and lower bias. Moreover, the data suggest that the diagnostic accuracy of a 10-min static 18F-FE-PE2I scan is non-inferior compared with 123I-FP-CIT scan used in standard clinical practice.

Whole liver segmentation based on deep learning and manual adjustment for clinical use in SIRT.

PURPOSE: In selective internal radiation therapy (SIRT), an accurate total liver segmentation is required for activity prescription and absorbed dose calculation. Our goal was to investigate the feasibility of using automatic liver segmentation based on a convolutional neural network (CNN) for CT imaging in SIRT, and the ability of CNN to reduce inter-observer variability of the segmentation. METHODS: A multi-scale CNN was modified for liver segmentation for SIRT patients. The CNN model was trained with 139 datasets from three liver segmentation challenges and 12 SIRT patient datasets from our hospital. Validation was performed on 13 SIRT datasets and 12 challenge datasets. The model was tested on 40 SIRT datasets. One expert manually delineated the livers and adjusted the liver segmentations from CNN for 40 test SIRT datasets. Another expert performed the same tasks for 20 datasets randomly selected from the 40 SIRT datasets. The CNN segmentations were compared with the manual and adjusted segmentations from the experts. The difference between the manual segmentations was compared with the difference between the adjusted segmentations to investigate the inter-observer variability. Segmentation difference was evaluated through dice similarity coefficient (DSC), volume ratio (RV), mean surface distance (MSD), and Hausdorff distance (HD). RESULTS: The CNN segmentation achieved a median DSC of 0.94 with the manual segmentation and of 0.98 with the manually corrected CNN segmentation, respectively. The DSC between the adjusted segmentations is 0.98, which is 0.04 higher than the DSC between the manual segmentations. CONCLUSION: The CNN model achieved good liver segmentations on CT images of good image quality, with relatively normal liver shapes and low tumor burden. 87.5% of the 40 CNN segmentations only needed slight adjustments for clinical use. However, the trained model failed on SIRT data with low dose or contrast, lesions with large density difference from their surroundings, and abnormal liver position and shape. The abovementioned scenarios were not adequately represented in the training data. Despite this limitation, the current CNN is already a useful clinical tool which improves inter-observer agreement and therefore contributes to the standardization of the dosimetry. A further improvement is expected when the CNN will be trained with more data from SIRT patients.

Comparative study of iodine-123-labeled hypericin and (99m)Tc-labeled hexakis [2-methoxy isobutyl isonitrile] in a rabbit model of myocardial infarction.

Identification of myocardial infarction (MI) by imaging is critical for clinical management of ischemic heart disease. Iodine-123-labeled hypericin (¹²³I-Hyp) is a new potent infarct avid agent. We sought to compare target selectivity and organ distribution between ¹²³I-Hyp and the myocardial perfusion agent, technetium-99m-labeled hexakis [2-methoxy isobutyl isonitrile] ((99m)Tc-Sestamibi) in rabbits with acute MI. Hypericin was radiolabeled with I using iodogen as oxidant, and (99m)Tc-Sestamibi was prepared from a commercial kit and radioactive sodium pertechnetate. Rabbits (n = 6) with 24-hour-old MI received ¹²³I-Hyp intravenously and received (99m)Tc-Sestamibi 9 hours later. They were studied by dual-isotope simultaneous acquisition micro single photon emission computed tomography/computed tomography (DISA-µSPECT/CT), tissue gamma counting (TGC), autoradiography, and histology. After purification, ¹²³I-Hyp was obtained with radiochemical purity around 99%. DISA-µSPECT/CT images showed ¹²³I-Hyp retention in infarcted but not in normal myocardium. By TGC, accumulation values reached 1.175 ± 0.096 percentage of injected dose per gram (%ID/g) and 0.028 ± 0.007%ID/g in infarcted myocardium and normal myocardium with high tracer concentration in liver, intestines, and gallbladder. (99m)Tc-Sestamibi was prepared with radiochemical purity over 95%. DISA-µSPECT/CT showed no accumulation in MI and high initial radioactivity levels in normal myocardium that were rapidly cleared as confirmed by TGC (0.011 ± 0.003%ID/g). Liver and intestines were clearly visualized. By TGC, gallbladder and kidneys show moderate (99m)Tc-Sestamibi uptake. The selectivity of ¹²³I-Hyp for infarcted myocardium and (99m)Tc-Sestamibi for normal myocardium was confirmed. ¹²³I-Hyp distribution in rabbits is characterized by hepatobiliary excretion. (99m)Tc-Sestamibi undergoes hepatorenal elimination.

An experimental survey of metal artefact reduction in computed tomography.

We present a survey of techniques for the reduction of streaking artefacts caused by metallic objects in X-ray Computed Tomography (CT) images. A comprehensive review of the existing state-of-the-art Metal Artefact Reduction (MAR) techniques, drawn predominantly from the medical CT literature, is supported by an experimental comparison of twelve MAR techniques. The experimentation is grounded in an evaluation based on a standard scientific comparison protocol for MAR methods, using a software generated medical phantom image as well as a clinical CT scan. The experimentation is extended by considering novel applications of CT imagery consisting of metal objects in non-tissue surroundings acquired from the aviation security screening domain. We address the shortage of thorough performance analyses in the existing MAR literature by conducting a qualitative as well as quantitative comparative evaluation of the selected techniques. We find that the difficulty in generating accurate priors to be the predominant factor limiting the effectiveness of the state-of-the-art medical MAR techniques when applied to non-medical CT imagery. This study thus extends previous works by: comparing several state-of-the-art MAR techniques; considering both medical and non-medical applications and performing a thorough performance analysis, considering both image quality as well as computational demands.

The SNR of time-of-flight positron emission tomography data for joint reconstruction of the activity and attenuation images.

Objective.Measurement of the time-of-flight (TOF) difference of each coincident pair of photons increases the effective sensitivity of positron emission tomography (PET). Many authors have analyzed the benefit of TOF for quantification and hot spot detection in the reconstructed activity images. However, TOF not only improves the effective sensitivity, it also enables the joint reconstruction of the tracer concentration and attenuation images. This can be used to correct for errors in CT- or MR-derived attenuation maps, or to apply attenuation correction without the help of a second modality. This paper presents an analysis of the effect of TOF on the variance of the jointly reconstructed attenuation and (attenuation corrected) tracer concentration images.Approach.The analysis is performed for PET systems that have a distribution of possibly non-Gaussian TOF-kernels, and includes the conventional Gaussian TOF-kernel as a special case. Non-Gaussian TOF-kernels are often observed in novel detector designs, which make use of two (or more) different mechanisms to convert the incoming 511 keV photon to optical photons. The analytical result is validated with a simple 2D simulation.Main results.We show that if two different TOF-kernels are equivalent for image reconstruction with known attenuation, then they are also equivalent for joint reconstruction of the activity and the attenuation images. The variance increase in the activity, caused by also jointly reconstructing the attenuation image, vanishes when the TOF-resolution approaches perfection.Significance.These results are of interest for PET detector development and for the development of stand-alone PET systems.

The SNR of Positron Emission Data With Gaussian and Non-Gaussian Time-of-Flight Kernels, With Application to Prompt Photon Coincidence.

It is well known that measurement of the time-of-flight (TOF) increases the information provided by coincident events in positron emission tomography (PET). This information increase propagates through the reconstruction and improves the signal-to-noise ratio in the reconstructed images. Takehiro Tomitani has analytically computed the gain in variance in the reconstructed image, provided by a particular TOF resolution, for the center of a uniform disk and for a Gaussian TOF kernel. In this paper we extend this result, by computing the signal-to-noise ratio (SNR) contributed by individual coincidence events for two different tasks. One task is the detection of a hot spot in the center of a uniform cylinder. The second one is the same as that considered by Tomitani, i.e. the reconstruction of the central voxel in the image of a uniform cylinder. In addition, we extend the computation to non-Gaussian TOF kernels. It is found that a modification of the TOF-kernel changes the SNR for both tasks in almost exactly the same way. The proposed method can be used to compare TOF-systems with different and possibly event-dependent TOF-kernels, as encountered when prompt photons, such as Cherenkov photons are present, or when the detector is composed of different scintillators. The method is validated with simple 2D simulations and illustrated by applying it to PET detectors producing optical photons with event-dependent timing characteristics.

Metal artifact reduction in computed tomography using local models in an image block-iterative scheme.

PURPOSE: In iterative reconstruction, metal artifacts can be reduced by applying more accurate reconstruction models that are usually also more computationally demanding. The hypothesis of this work is that these complex models only need to be applied in the vicinity of the metals and that a less complex model can be used for the remainder of the reconstruction volume. METHODS: A method is described that automatically divides the reconstruction volume into metal and nonmetal regions. The different regions are called patches. A different energy and resolution model can be assigned to each of the patches. The patches containing metals are reconstructed with a fully polychromatic spectral model (IMPACT) and if necessary with an increased resolution model. The patch without metals is reconstructed with a simple polychromatic model (MLTRC) that only includes the spectral behavior of water attenuation. Comparing the computational complexity of IMPACT and MLTRC gives a ratio of 8:3. The different patches are updated sequentially as in a grouped coordinate algorithm. Two phantoms were simulated and measured: a circular phantom containing small metal cylinders and a body phantom representing a human pelvis with two femoral implants. As a first test, the sequential update of the patches was applied while using the same energy model for all patches. Second, the local model approach was applied using MLTRC for nonmetal regions and IMPACT for metal regions. The results of different iterative reconstruction schemes are compared to the results of projection completion, another important method for the reduction of metal artifacts. RESULTS: Reconstruction schemes including the sequential update of the patches result in images with less streak artifacts compared to a regular reconstruction. The sequential update of each of the metal regions improves the relative convergence of the metals (edges and attenuation values) against the rest of the image, which leads to an improved artifact reduction. Using the combined IMPACT+MLTRC model results in a similar image quality as using IMPACT everywhere, while providing an important benefit regarding computational complexity. Some streak and shadow artifacts were still present, but all structures present in the phantom could be observed. Projection completion results in reconstructions with less obvious streak and shadow artifacts but tends to deform or erase structures lying close to or in between metallic structures. CONCLUSIONS: Metal artifact reduction with iterative reconstruction can be achieved by using complex models only locally without losing image quality. Separately updating metal regions leads to reduced streak artifacts. Structures lying close to or in between metals are often better reconstructed, compared to projection completion results, because all available information is used.

Low-dose CT allows for accurate proton therapy dose calculation and plan optimization.

Objective.Protons offer a more conformal dose delivery compared to photons, yet they are sensitive to anatomical changes over the course of treatment. To minimize range uncertainties due to anatomical variations, a new CT acquisition at every treatment session would be paramount to enable daily dose calculation and subsequent plan adaptation. However, the series of CT scans results in an additional accumulated patient dose. Reducing CT radiation dose and thereby decreasing the potential risk of radiation exposure to patients is desirable, however, lowering the CT dose results in a lower signal-to-noise ratio and therefore in a reduced quality image. We hypothesized that the signal-to-noise ratio provided by conventional CT protocols is higher than needed for proton dose distribution estimation. In this study, we aim to investigate the effect of CT imaging dose reduction on proton therapy dose calculations and plan optimization.Approach.To verify our hypothesis, a CT dose reduction simulation tool has been developed and validated to simulate lower-dose CT scans from an existing standard-dose scan. The simulated lower-dose CTs were then used for proton dose calculation and plan optimization and the results were compared with those of the standard-dose scan. The same strategy was adopted to investigate the effect of CT dose reduction on water equivalent thickness (WET) calculation to quantify CT noise accumulation during integration along the beam.Main results.The similarity between the dose distributions acquired from the low-dose and standard-dose CTs was evaluated by the dose-volume histogram and the 3D Gamma analysis. The results on an anthropomorphic head phantom and three patient cases indicate that CT imaging dose reduction up to 90% does not have a significant effect on proton dose calculation and plan optimization. The relative error was employed to evaluate the similarity between WET maps and was found to be less than 1% after reducing the CT imaging dose by 90%.Significance.The results suggest the possibility of using low-dose CT for proton therapy dose estimation, since the dose distributions acquired from the standard-dose and low-dose CTs are clinically equivalent.

Design and modeling of a high resolution and high sensitivity PET brain scanner with double-ended readout.

In the wake of recent advancements in scintillator, photodetector, and low-noise fast electronics technologies, as well as in fast reconstruction software, positron emission tomography (PET) scanners have seen considerable improvements in spatial resolution, time resolution, and absolute sensitivity. To continue this trend, we present a helmet type PET brain scanner design that combines high solid angle coverage and double-ended readout of 30 mm-thick scintillator crystals to achieve excellent absolute sensitivity, depth of interaction resolution, and time resolution. This scanner comprises 598 detector arrays, each with 8 × 8 Lu1.8Y0.2SiO5:Ce (LYSO:Ce) crystals with dimensions 3.005 × 3.005 × 30 mm3one-to-one coupled on either end to silicon photomultipliers (SiPMs). Our Monte Carlo simulations based in the platform Geant4 predict that this scanner would attain an absolute sensitivity to a 35 cm line source placed at the center of the radial field of view of (17.1 ± 0.1)%, a depth of interaction resolution of (3.99 ± 0.05) mm, and a coincidence time resolution of (198 ± 5) ps. Our simulations also predict radial, tangential, and axial spatial resolutions at the center of the field of view of 3.3 mm, 3.1 mm, and 3.3 mm, respectively. As this set of simultaneous parameters compares favorably to today's most advanced clinical PET scanners and other proposed designs, this scanner has a good chance of becoming a preferred tool for high quality brain imaging.

Segmentation-guided multi-modal registration of liver images for dose estimation in SIRT.

PURPOSE: Selective internal radiation therapy (SIRT) requires a good liver registration of multi-modality images to obtain precise dose prediction and measurement. This study investigated the feasibility of liver registration of CT and MR images, guided by segmentation of the liver and its landmarks. The influence of the resulting lesion registration on dose estimation was evaluated. METHODS: The liver segmentation was done with a convolutional neural network (CNN), and the landmarks were segmented manually. Our image-based registration software and its liver-segmentation-guided extension (CNN-guided) were tuned and evaluated with 49 CT and 26 MR images from 20 SIRT patients. Each liver registration was evaluated by the root mean square distance (RMSD) of mean surface distance between manually delineated liver contours and mass center distance between manually delineated landmarks (lesions, clips, etc.). The root mean square of RMSDs (RRMSD) was used to evaluate all liver registrations. The CNN-guided registration was further extended by incorporating landmark segmentations (CNN&LM-guided) to assess the value of additional landmark guidance. To evaluate the influence of segmentation-guided registration on dose estimation, mean dose and volume percentages receiving at least 70 Gy (V70) estimated on the 99mTc-labeled macro-aggregated albumin (99mTc-MAA) SPECT were computed, either based on lesions from the reference 99mTc-MAA CT (reference lesions) or from the registered floating CT or MR images (registered lesions) using the CNN- or CNN&LM-guided algorithms. RESULTS: The RRMSD decreased for the floating CTs and MRs by 1.0 mm (11%) and 3.4 mm (34%) using CNN guidance for the image-based registration and by 2.1 mm (26%) and 1.4 mm (21%) using landmark guidance for the CNN-guided registration. The quartiles for the relative mean dose difference (the V70 difference) between the reference and registered lesions and their correlations [25th, 75th; r] are as follows: [- 5.5% (- 1.3%), 5.6% (3.4%); 0.97 (0.95)] and [- 12.3% (- 2.1%), 14.8% (2.9%); 0.96 (0.97)] for the CNN&LM- and CNN-guided CT to CT registrations, [- 7.7% (- 6.6%), 7.0% (3.1%); 0.97 (0.90)] and [- 15.1% (- 11.3%), 2.4% (2.5%); 0.91 (0.78)] for the CNN&LM- and CNN-guided MR to CT registrations. CONCLUSION: Guidance by CNN liver segmentations and landmarks markedly improves the performance of the image-based registration. The small mean dose change between the reference and registered lesions demonstrates the feasibility of applying the CNN&LM- or CNN-guided registration to volume-level dose prediction. The CNN&LM- and CNN-guided registrations for CTs can be applied to voxel-level dose prediction according to their small V70 change for most lesions. The CNN-guided MR to CT registration still needs to incorporate landmark guidance for smaller change of voxel-level dose estimation.

Experimental validation of a rodent PET scanner prototype based on a single LYSO crystal tube.

Improving sensitivity and spatial resolution in small animal Positron Emission Tomography imaging instrumentation constitutes one of the main goals of nuclear imaging research. These parameters are degraded by the presence of gaps between the detectors. The present manuscript experimentally validates our prototype of an edge-less pre-clinical PET system based on a single LYSO:Ce annulus with an inner diameter of 62 mm and 10 outer facets of 26 × 52 mm2. Scintillation light is read out by arrays of 8 × 8 SiPMs coupled to the facets, using a projection readout of the rows and columns signals. The readout provides accurate Depth of Interaction (DOI). We have implemented a calibration that mitigates the DOI-dependency of the transaxial and axial impact coordinates, and the energy photopeak gain. An energy resolution of 23.4 ± 1.8% was determined. Average spatial resolution of 1.4 ± 0.2 and 1.3 ± 0.4 mm FWHM were achieved for the radial and axial directions, respectively. We found a peak sensitivity of 3.8% at the system center, and a maximum NECR at 40.6 kcps for 0.27 mCi. The image quality was evaluated using reconstructed images of an array of sources and the NEMA image quality phantom was also studied.

An optically-guided cochlear implant sheath for real-time monitoring of electrode insertion into the human cochlea.

In cochlear implant surgery, insertion of perimodiolar electrode arrays into the scala tympani can be complicated by trauma or even accidental translocation of the electrode array within the cochlea. In patients with partial hearing loss, cochlear trauma can not only negatively affect implant performance, but also reduce residual hearing function. These events have been related to suboptimal positioning of the cochlear implant electrode array with respect to critical cochlear walls of the scala tympani (modiolar wall, osseous spiral lamina and basilar membrane). Currently, the position of the electrode array in relation to these walls cannot be assessed during the insertion and the surgeon depends on tactile feedback, which is unreliable and often comes too late. This study presents an image-guided cochlear implant device with an integrated, fiber-optic imaging probe that provides real-time feedback using optical coherence tomography during insertion into the human cochlea. This novel device enables the surgeon to accurately detect and identify the cochlear walls ahead and to adjust the insertion trajectory, avoiding collision and trauma. The functionality of this prototype has been demonstrated in a series of insertion experiments, conducted by experienced cochlear implant surgeons on fresh-frozen human cadaveric cochleae.

Can nuclear imaging accurately detect scar in ischemic cardiac resynchronization therapy candidates?

BACKGROUND: Accurate scar assessment is crucial in cardiac resynchronization therapy (CRT) candidates, since its presence is a negative predictor for CRT response. Therefore, we assessed the performance of different PET parameters to detect scar in CRT candidates. METHODS: Twenty-nine CRT candidates underwent 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT), resting 13N-NH3-PET/CT and cardiac magnetic resonance (CMR) prior to CRT implantation. Segmental 18F-FDG uptake, late 13N-NH3 uptake and absolute myocardial blood flow (MBF) were evaluated for scar detection using late gadolinium enhancement (LGE) CMR as reference. A receiver operator characteristic (ROC) area under the curve (AUC) ≥0.8 indicated a good accuracy of the methods evaluated. RESULTS: Scar was present in 111 of 464 segments. None of the approaches could reliably identify segments with nontransmural scar, except for 18F-FDG uptake in the lateral wall (AUC 0.83). Segmental transmural scars could be detected with all methods (AUC ≥ 0.8), except for septal 18F-FDG uptake and MBF in the inferior wall (AUC < 0.8). Late 13N-NH3 uptake was the best parameter for transmural scar detection, independent of its location, with a sensitivity of 80% and specificity of 92% using a cutoff of 66% of the maximum tracer activity. CONCLUSIONS: Late 13N-NH3 uptake is superior to 13N-NH3 MBF and 18F-FDG in detecting transmural scar, independently of its location. However, none of the tested PET parameters was able to accurately detect nontransmural scar.

A dual-targeting anticancer approach: soil and seed principle.

PURPOSE: To test the hypothesis that targeting the microenvironment (soil) may effectively kill cancer cells (seeds) through a small-molecular weight sequential dual-targeting theragnostic strategy, or dual-targeting approach. MATERIALS AND METHODS: With approval from the institutional animal care and use committee, 24 rats were implanted with 48 liver rhabdomyosarcomas (R1). First, the vascular-disrupting agent combretastatin A4 phosphate (CA4P) was injected at a dose of 10 mg/kg to cause tumor necrosis, which became a secondary target. Then, the necrosis-avid agent hypericin was radiolabeled with iodine 131 to form (131)I-hypericin, which was injected at 300 MBq/kg 24 hours after injection of CA4P. Both molecules have small molecular weight, are naturally or synthetically derivable, are intravenously injectable, and are of unique targetablities. The tumor response in the dual-targeting group was compared with that in vehicle-control and single-targeting (CA4P or (131)I-hypericin) groups with in vivo magnetic resonance imaging and scintigrams and ex vivo gamma counting, autoradiography, and histologic analysis. Tumor volumes, tumor doubling time (TDT), and radiobiodistribution were analyzed with statistical software. P values below .05 were considered to indicate a significant difference. RESULTS: Eight days after treatment, the tumor volume of rhabdomyosarcoma in the vehicle-control group was double that in both single-targeting groups (P < .001) and was five times that in the dual-targeting group (P < .0001), without treatment-related animal death. The TDT was significantly longer in the dual-targeting group (P < .0001). Necrosis appeared as hot spots on scintigrams, corresponding to 3.13% of the injected dose of (131)I-hypericin per gram of tissue (interquartile range, 2.92%-3.97%) and a target-to-liver ratio of 20. The dose was estimated to be 100 times the cumulative dose of 50 Gy needed for radiotherapeutic response. Thus, accumulated (131)I-hypericin from CA4P-induced necrosis killed residual cancer cells with ionizing radiation and inhibited tumor regrowth. CONCLUSION: This dual-targeting approach may be a simple and workable solution for cancer treatment and deserves further exploitation.

Do androgens control the uptake of 18F-FDG, 11C-choline and 11C-acetate in human prostate cancer cell lines?

PURPOSE: The aim of this study was to evaluate the impact of androgen ablation therapy in different prostate cancer (PCa) cell lines--reflecting different stages of the disease--on (18)F-fluorodeoxyglucose (FDG), 11C-choline and 11C-acetate uptake. METHODS: Uptake experiments were performed in androgen-sensitive (LNCaP, PC346C) and independent cell lines (22Rv1, PC346DCC, PC-3) as well as in a benign prostatic hyperplasia (BPH-1) cell line. Tracer uptake was assessed under androgen ablation. Results of the cancer cell lines were normalized to those of BPH-1. To evaluate the effect of androgen on the uptake of 18F-FDG, 11C-choline and 11C-acetate in PCa cell lines, 10(-8) M R1881, 10(-10) M R1881, the combination of 10(-10) M R1881 plus 10(-6) M Casodex or 10(-6) M Casodex alone were added in parallel cell cultures 1 day before uptake experiments. Uptake in androgen-supplemented cell cultures was compared to the uptake under androgen deprivation. Uptake was corrected for cell number using protein content. RESULTS: Compared to BPH-1, a higher 18F-FDG uptake was observed only in PC346C cells, whereas a higher 11C-choline and markedly increased 11C-acetate uptake was seen in all cancer cell lines. Androgens significantly modulated the uptake of 18F-FDG in LNCaP, PC346C and 22Rv1 cells, and of 11C-choline in the PC346C and 22Rv1 cell line. No androgenic effect on 11C-choline and 18F-FDG uptake was observed in PC-3 and PC346DCC cells. 11C-Acetate uptake was independent of androgen status in all PCa cell lines studied. CONCLUSION: 18F-FDG uptake in PCa cell lines showed the highest variability and strongest androgen effect, suggesting its poor potential for metabolic imaging of advanced PCa. In contrast to 18F-FDG and 11C-choline, 11C-acetate uptake was unaffected by androgens and thus 11C-acetate seems best for monitoring PCa progression.