The clinical application of PET/CT: a contemporary review

The combination of positron emission tomography (PET) scanners and x-ray computed tomography (CT) scanners into a single PET/CT scanner has resulted in vast improvements in the diagnosis of disease, particularly in the field of oncology. A decade on from the publication of the details of the first PET/CT scanner, we review the technology and applications of the modality. We examine the design aspects of combining two different imaging types into a single scanner, and the artefacts produced such as attenuation correction, motion and CT truncation artefacts. The article also provides a discussion and literature review of the applications of PET/CT to date, covering detection of tumours, radiotherapy treatment planning, patient management, and applications external to the field of oncology

Iodine-123 labeled reboxetine analogues for imaging of noradrenaline transporter in brain using single photon emission computed tomography

Preliminary investigation of the radioiodinated (S,S)-reboxetine analogue, 123I-INER, in baboons showed this tracer to have promise for imaging the noradrenaline transporter (NAT) using single photon emission computed tomography (SPECT). More recently, the radioiodinated (R,S)-stereoisomer of 123I-INER, 123I-NKJ64, has been synthesized and preliminary evaluation in rats has been reported. This article reports the brain distribution and pharmacokinetic properties of 123I-NKJ64 in baboons and compares results with 123I-INER data in the same species. SPECT studies were conducted in two ovariectomized adult female baboons using two different protocols: (1) bolus of 123I-INER or 123I-NKJ64; and (2) bolus plus constant infusion of 123I-NKJ64 with reboxetine (2.0 mg/kg) administration at equilibrium. Following bolus injection, both radiotracers rapidly and avidly entered the baboon brain. The regional brain accumulation of 123I-NKJ64 did not match the known distribution of NAT in baboon brain, contrasting with previous results obtained in rats. Conversely, the regional distribution of 123I-INER was consistent with known distribution of NAT in baboon brain. No displacement of 123I-NKJ64 was observed following administration of reboxetine. This contrasts with previous data obtained for 123I-INER, where 60% of specific binding was displaced by a lower dose of reboxetine. These data suggest that 123I-NKJ64 may lack affinity and selectivity for NAT in baboon brain and 123I-INER is the most promising iodinated reboxetine analogue developed to date for in vivo imaging of NAT in brain using SPECT. This study highlights the importance of species differences during radiotracer development and the stereochemical configuration of analogues of reboxetine in vivo. Synapse, 2012. -® 2012 Wiley Periodicals, In

The Performance of MLEM for Dynamic Imaging From Simulated Few-View, Multi-Pinhole SPECT

Stationary small-animal SPECT systems are being developed for rapid dynamic imaging from limited angular views. This work quantified, through simulations, the performance of Maximum Likelihood Expectation Maximization (MLEM) for reconstructing a time-activity curve (TAC) with uptake duration of a few seconds from a stationary, three-camera multi-pinhole SPECT system. The study also quantified the benefits of a heuristic method of initializing the reconstruction with a prior image reconstructed from a conventional number of views, for example from data acquired during the late-study portion of the dynamic TAC. We refer to MLEM reconstruction initialized by a prior-image initial guess (IG) as MLEMig. The effect of the prior-image initial guess on the depiction of contrast between two regions of a static phantom was quantified over a range of angular sampling schemes. A TAC was modeled from the experimentally measured uptake of 99mTc-hexamethylpropyleneamine oxime (HMPAO) in the rat lung. The resulting time series of simulated images was quantitatively analyzed with respect to the accuracy of the estimated exponential washin and washout parameters. In both static and dynamic phantom studies, the prior-image initial guess improved the spatial depiction of the phantom, for example improved definition of the cylinder boundaries and more accurate quantification of relative contrast between cylinders. For example in the dynamic study, there was ~ 50% error in relative contrast for MLEM reconstructions compared to ~ 25-30% error for MLEMig. In the static phantom study, the benefits of the initial guess decreased as the number of views increased. The prior-image initial guess introduced an additive offset in the reconstructed dynamic images, likely due to biases introduced by the prior image. MLEM initialized with a uniform initial guess yielded images that faithfully reproduced the time dependence of the simulated TAC; there were no s- atistically significant differences in the mean exponential washin/washout parameters estimated from MLEM reconstructions compared to the true values. Washout parameters estimated from MLEMig reconstructions did not differ significantly from the true values, however the estimated washin parameter differed significantly from the true value in some cases. Overall, MLEM reconstruction from few views and a uniform initial guess accurately quantified the time dependance of the TAC while introducing errors in the spatial depiction of the object. Initializing the reconstruction with a late-study initial guess improved spatial accuracy while decreasing temporal accuracy in some cases

Implementation of absolute quantification in small-animal SPECT imaging: Phantom and animal studies

Purpose: Presence of photon attenuation severely challenges quantitative accuracy in single-photon emission computed tomography (SPECT) imaging. Subsequently, various attenuation correction methods have been developed to compensate for this degradation. The present study aims to implement an attenuation correction method and then to evaluate quantification accuracy of attenuation correction in small-animal SPECT imaging. Methods: Images were reconstructed using an iterative reconstruction method based on the maximum-likelihood expectation maximization (MLEM) algorithm including resolution recovery. This was implemented in our designed dedicated small-animal SPECT (HiReSPECT) system. For accurate quantification, the voxel values were converted to activity concentration via a calculated calibration factor. An attenuation correction algorithm was developed based on the first-order Chang’s method. Both phantom study and experimental measurements with four rats were used in order to validate the proposed method. Results: The phantom experiments showed that the error of �15.5% in the estimation of activity concentration in a uniform region was reduced to +5.1% when attenuation correction was applied. For in vivo studies, the average quantitative error of �22.8 � 6.3% (ranging from �31.2% to �14.8%) in the uncorrected images was reduced to +3.5 � 6.7% (ranging from �6.7 to +9.8%) after applying attenuation correction. Conclusion: The results indicate that the proposed attenuation correction algorithm based on the first-order Chang’s method, as implemented in our dedicated small-animal SPECT system, significantly improves accuracy of the quantitative analysis as well as the absolute quantification

ATTENUATION CORRECTION IN CARDIAC PET/CT USING A TIME- AVERAGED CT

Heart disease is a leading cause of death in Canada, and Positron Emission Tomography (PET) is the gold standard for determining the viability of heart tissue following a heart attack. PET images require correction for attenuation, that is, for signal absorption by patient tissues. Attenuation correction (AC), is done via a transmission scan such as Computed Tomography (CT). However, due to the differences between PET and CT scan durations, respiration-induced motion can cause temporal mismatches leading to errors in the reconstructed PET image. This study compares the magnitude of these errors when single-phase CT, respiratory-averaged CT, and 4D CT are used for AC of cardiac PET in an in vivo canine model. The respiratory-averaged CT correction produced maximum percentage differences that were 7 times less than those produced by the single-phase correction. Using a respiratory-averaged CT may provide an accurate form of AC for cardiac PET imaging

Computed tomography in veterinary medicine: currently published and tomorrow’s vision

The utilisation of Computed Tomography (CT) in veterinary practice has been increasing rapidly in line with reduced cost, improved availability and the increase in expertise and technology. This review briefly examines the recent technological advancements in imaging in the veterinary sector, and explores how CT and micro-CT (μCT) have furthered basic understanding and knowledge, and influenced clinical practice and medicine. The uses of CT technology in veterinary research, especially in relation to bone, vasculature and soft tissues, are explored and compared in relation to the different species. CT is essential not only for the diagnosis and treatment of many disorders, but it is now being used to understand areas ranging from drug delivery and surgical advancements through to anatomical and educational uses throughout the world

Development of Pinhole X-ray Fluorescence Imaging System to Measure in vivo Biodistribution of Gold Nanoparticles

학위논문(박사)--서울대학교 대학원 :융합과학기술대학원 융합과학부,2019. 8. 예성준.목적: 본 연구의 목표는 금나노입자의 체내 농도 분포 측정을 위한 핀홀 엑스선 형광 영상시스템을 개발하고, 시간에 따른 쥐의 체내 금나노입자 분포 영상을 획득하여 개발 영상시스템이 전임상시험에 활용 가능함을 실험적으로 증명하는 것이다. 2차원 cadmium zinc telluride (CZT) 감마 카메라를 사용하여 K-shell 엑스선 형광 신호를 측정함으로써, 영상 획득 시간과 피폭 방사선량을 줄일 수 있다. 또한, 본 연구는 샘플의 복잡한 전처리 과정 없이 금나노입자의 체외 농도를 측정할 수 있는 silicon drift detector (SDD)를 사용한 L-shell 엑스선 형광 측정 시스템을 개발하고자 한다. 방법: 금나노입자의 농도와 K-shell 엑스선 형광 신호 사이의 교정 곡선을 획득하기 위해 0.0 wt%, 0.125 wt%, 0.25 wt%, 0.5 wt%, 1.0 wt%, 2.0 wt%의 금나노입자 샘플을 반지름 2.5 cm인 아크릴 팬톰에 삽입하여 140 kVp 엑스선을 1분씩 조사하였다. K-shell 엑스선 형광 신호는 금나노입자가 삽입되어 있는 아크릴 팬톰으로부터 측정한 엑스선 스펙트럼에서 금나노입자가 삽입되어 있지 않은 아크릴 팬톰으로부터 측정한 엑스선 스펙트럼의 차이를 통해 추출하였다. 금나노입자 주입 후 측정 데이터만으로 금나노입자의 엑스선 형광 영상을 획득하기 위해 인공지능 convolutional neural network (CNN) 모델을 개발하고 적용하였다. 실험용 쥐로부터 추출한 장기의 금나노입자 농도 측정을 위해 L-shell 엑스선 형광 시스템측정을 개발하였으며, 이 시스템은 SDD 측정기와 40 kVp의 선원을 이용하여 2.34 μg – 300 μg (금나노입자)/30 mg (물) (0.0078 wt%-1.0 wt%)의 금나노입자와 L-shell 엑스선 형광 신호 사이의 교정 곡선을 얻어 장기 내 축적된 금나노입자의 질량을 측정하였다. 핀홀 엑스선 형광 영상시스템을 이용하여 실험용 쥐에 금나노입자를 주입 후 시간에 따른 신장 내 금나노입자 농도 영상을 획득하였다. 안락사 후 적출한 양쪽 신장, 간, 비장, 혈액의 금나노입자 농도를 L-shell 엑스선 형광 체외 측정 시스템과 ICP-AES를 사용하여 측정하였고 영상시스템을 통해 획득한 농도와 비교·검증하였다. 영상 획득 시 실험용 쥐에 조사되는 방사선량은 TLD를 실험용 쥐의 피부에 붙여 측정하였다. 결과: 엑스선 형광 영상 분석을 통해 측정한 실험용 쥐의 오른쪽 신장 내 금나노입자의 농도는 주입 직후 1.58±0.15 wt%였으며, 60분 후 그 농도는 0.77±0.29 wt%로 감소하였다. 개발한 인공지능 CNN 모델을 적용해 금나노입자 주입 전 영상의 획득 없이 금나노입자의 엑스선 형광 영상을 생성할 수 있었다. 적출한 장기에서 측정된 금나노입자의 신장 내 농도는 L-shell 엑스선 형광 측정법으로 0.96±0.22 wt%, ICP-AES로는 1.00±0.50 wt% 였다. 영상 획득 시 실험용 쥐의 피부에 전달된 방사선량은 금나노입자 주입 전과 후 영상을 모두 획득 시(총 2분) 107±4 mGy, CNN 모델 적용 시(1분) 53±2 mGy로 측정되었다. 결론: 2차원 CZT 감마 카메라와 핀홀 콜리메이터를 사용한 엑스선 형광 영상시스템은 영상 획득 시간과 피폭 방사선량을 크게 감소시켰으며, 살아있는 쥐의 시간에 따른 체내 금나노입자 분포 변화를 영상화 할 수 있음을 증명하였다. 또한 L-shell 엑스선 형광 측정 시스템은 복잡한 전처리 과정 없이 체외 금나노입자의 농도를 정확하게 측정할 수 있었다. 본 개발 시스템을 금속나노입자의 체내 분포 연구를 위한 전임상시험용 분자영상장비로서 활용할 수 있을 것으로 기대한다.Purpose: This work aims to show the experimental feasibility for a dynamic in vivo X-ray fluorescence (XRF) imaging of gold in living mice exposed to gold nanoparticles (GNPs) using polychromatic X-rays. By collecting K-shell XRF photons using a 2D cadmium zinc telluride (CZT) gamma camera, the imaging system was expected to have a short image acquisition time and deliver a low radiation dose. This study also investigated the feasibility of using an L-shell XRF detection system with a single-pixel silicon drift detector (SDD) to measure ex vivo GNP concentrations from biological samples. Methods: Six GNP columns of 0 % by weight (wt%), 0.125 wt%, 0.25 wt%, 0.5 wt%, 1.0 wt% and 2.0 wt% inserted in a 2.5 cm diameter polymethyl methacrylate (PMMA) phantom were used for acquiring a linear regression curve between the concentrations of GNPs and the K-shell XRF photons emitted from GNPs. A fan-beam of 140 kVp X-rays irradiated the phantom for 1 min in each GNP sample. The photon spectra were measured by the CZT gamma camera. The K-shell XRF counts were derived by subtracting the photon counts of the 0 wt% PMMA phantom (i.e., pre-scanning) from the photon counts of the GNP-loaded phantom (i.e., post-scanning). Furthermore, a 2D convolutional neural network (CNN) was applied to generate the K-shell XRF counts from the post-scanned data without the pre-scanning. For a more sensitive detection of the ex vivo concentrations of GNPs in the biological samples, the L-shell XRF detection system using the single-pixel SDD was developed. Six GNP samples of 2.34 μg–300 μg Au/30 mg water (i.e., 0.0078 wt%–1.0 wt% GNPs) were used for acquiring a calibration curve to correlate the GNP mass to the L-shell XRF counts. The kidney slices of three Balb/C mice were scanned at various periods after the injection of GNPs in order to acquire the quantitative information of GNPs. The concentrations of GNPs measured by the CZT gamma camera and the SDD were cross-compared and then validated by inductively coupled plasma atomic emission spectroscopy (ICP-AES). The radiation dose was assessed by the measurement of TLDs attached to the skin of the mice. Results: The K-shell XRF images showed that the concentration of GNPs in the right kidneys from the mice was 1.58±0.15 wt% at T = 0 min after the injection. At T = 60 min after the injection, the concentration of GNPs in the right kidneys was reduced to 0.77±0.29 wt%. The K-shell XRF images generated by the 2D CNN were similar to those derived by the direct subtraction method. The measured ex vivo concentration of GNPs was 0.96±0.22 wt% by the L-shell XRF detection system while it was 1.00±0.50 wt% by ICP-AES. The radiation dose delivered to the skin of the mice was 107±4 mGy for acquiring one slice image by using the direct subtraction method while it was 53±2 mGy by using the 2D CNN. Conclusions: A pinhole K-shell XRF imaging system with a 2D CZT gamma camera showed a dramatically reduced scan time and delivered a low radiation dose. Hence, a dynamic in vivo XRF imaging of gold in living mice exposed to GNPs was technically feasible in a benchtop configuration. In addition, an L-shell XRF detection system can be used to measure ex vivo concentrations of GNPs in biological samples. This imaging system could provide a potential in vivo molecular imaging for metal nanoparticles to emerge as a radiosensitizer and a drug-delivery agent in preclinical studies.CHAPTER I. INTRODUCTION 1 I.1 Applications of Metal Nanoparticles in Medicine 1 I.2 Molecular Imaging of Metal Nanoparticles 3 I.3 X-ray Fluorescence Imaging 5 I.3.1 Principle of X-ray Fluorescence Imaging 5 I.3.2 History of X-ray Fluorescence Imaging 8 I.3.3 Specific Aims 12 CHAPTER II. MATERIAL AND METHODS 15 II.1 Monte Carlo Model 15 II.1.1 Geometry of Monte Carlo Simulations 15 II.1.2 Image Processing 21 II.1.3 Radiation Dose 27 II.2 Development of Pinhole K-shell XRF Imaging System 28 II.2.1 System Configuration and Operation Scheme 28 II.2.2 Pinhole K-shell XRF Imaging System 31 II.2.2.1 Experimental Setup 31 II.2.2.2 Measurement of K-shell XRF Signal 36 II.2.2.3 Signal Processing: Correction Factors 39 II.2.2.4 Application of Convolutional Neural Network 42 II.2.3 K-shell XRF Detection System 45 II.2.3.1 Experimental Setup 45 II.2.3.2 Signal Processing 47 II.2.4 L-shell XRF Detection System 49 II.2.4.1 Experimental Setup 49 II.2.4.2 Signal Processing 51 II.3 In vivo Study in Mice 53 II.3.1 Experimental Setup 53 II.3.2 Dose Measurement 56 CHAPTER III. RESULTS 57 III.1 Monte Carlo Model 57 III.1.1 Geometric Efficiency, System and Energy Resolution 57 III.1.2 K-shell XRF Image by Monte Carlo Simulations 59 III.1.3 Radiation Dose 69 III.2. Development of Pinhole XRF Imaging System 70 III.2.1 Pinhole K-shell XRF Imaging System 70 III.2.1.1 Energy Calibration and Measurement of Field Size 70 III.2.1.2 Raw K-shell XRF Signal 73 III.2.1.3 Correction Factors 78 III.2.1.4 K-shell XRF Image 81 III.2.2 K-shell XRF Detection System 85 III.2.3 L-shell XRF Detection System 89 III.3 In vivo Study in Mice 92 III.3.1 In vivo K-shell XRF Image 92 III.3.2 Quantification of GNPs in Living Mice 96 III.3.3 Dose Measurement 101 CHAPTER IV. DISCUSSION 102 IV.1 Monte Carlo Model 102 IV.2 Development of Pinhole K-shell XRF Imaging System 104 IV.2.1 Quantification of GNPs 105 IV.2.2 Comparison between MC and Experimental Results 107 IV.2.3 Limitations 108 IV.2.3.1 Concentration 108 IV.2.3.2 System Resolution 110 IV.2.3.3 Radiation Dose 111 IV.2.4 Application of CNN 112 IV.2.5 Future Work 114 CHAPTER V. CONCLUSIONS 115 REFERENCES 116 ABSTRACT (in Korean) 123Docto

Small-animal SPECT and SPECT/CT: application in cardiovascular research

Preclinical cardiovascular research using noninvasive radionuclide and hybrid imaging systems has been extensively developed in recent years. Single photon emission computed tomography (SPECT) is based on the molecular tracer principle and is an established tool in noninvasive imaging. SPECT uses gamma cameras and collimators to form projection data that are used to estimate (dynamic) 3-D tracer distributions in vivo. Recent developments in multipinhole collimation and advanced image reconstruction have led to sub-millimetre and sub-half-millimetre resolution SPECT in rats and mice, respectively. In this article we review applications of microSPECT in cardiovascular research in which information about the function and pathology of the myocardium, vessels and neurons is obtained. We give examples on how diagnostic tracers, new therapeutic interventions, pre- and postcardiovascular event prognosis, and functional and pathophysiological heart conditions can be explored by microSPECT, using small-animal models of cardiovascular disease