Single-photon Tomography Research Articles

The role of iodine-124 positron emission tomography in molecular imaging

Radioactive iodine has been, in various forms, the mainstay of Nuclear Medicine. Iodine-123 is the most widely used iodine isotope for single photon imaging. Iodine-125 continues to be used in diverse applications from in vitro radioassay to in vivo estimation of various pathophysiologic correlates. Iodine-131 (131I), useful for imaging as well as therapy, has contributed more than any other radionuclide to the growth and sustenance of Nuclear Medicine. Positron emission tomography (PET) is an indispensable tool in current clinical practice, spurred by the rapid and increasing availability of radiopharmaceuticals for in vivo imaging. Most clinical PET imaging utilizes fluorine-18; there is a need for positron emitters with longer half-lives, suitable for imaging larger molecules of interest. Iodine-124 (124I) has approximately 23 % positron emission; its 4-day half-life lends itself to sequential imaging, and its dosimetry is comparable to iodine-131. Iodine can be easily attached to a variety of molecules without alteration of physico-chemical or biologic properties. PET with 124I-labeled molecules enables longitudinal in vivo assessment of their distribution; such pharmacokinetic and biodistribution information has considerable utility in oncologic and non-oncologic applications. We will provide a clinical perspective on the physical and chemical characteristics of 124I, as the iodide, as well as radiolabeled to a wide variety of molecules of interest. Radioiodination is accomplished based on the chemical and biologic nature of the ligand to be studied, and issues of relevance will be highlighted. We will conclude by describing the current and potential future clinical applications of 124I-based tracers used for molecular imaging in diagnosis and therapy.

Deep imaging in scattering media with selective plane illumination microscopy.

In most biological tissues, light scattering due to small differences in refractive index limits the depth of optical imaging systems. Two-photon microscopy (2PM), which significantly reduces the scattering of the excitation light, has emerged as the most common method to image deep within scattering biological tissue. This technique, however, requires high-power pulsed lasers that are both expensive and difficult to integrate into compact portable systems. Using a combination of theoretical and experimental techniques, we show that if the excitation path length can be minimized, selective plane illumination microscopy (SPIM) can image nearly as deep as 2PM without the need for a high-powered pulsed laser. Compared to other single-photon imaging techniques like epifluorescence and confocal microscopy, SPIM can image more than twice as deep in scattering media ( ? 10 times the mean scattering length). These results suggest that SPIM has the potential to provide deep imaging in scattering media in situations in which 2PM systems would be too large or costly.

Bellini's duct carcinoma: A report of two cases and a review of the literature.

Bellini's duct carcinoma (BDC) is a rare and aggressive variant of renal cell carcinoma that possesses an extremely poor prognosis. The greater the grade or stage of disease, the poorer the prognosis tends to be. This study presents two cases of BDC; one case of low grade BDC and one case of high grade BDC in a 47-year-old male and 74-year-old female, respectively. The 47-year-old male patient presented with painless gross hematuria, which had lasted for 3 weeks and subsequently underwent purely laparoscopic nephroureterectomy. After 4-years of follow-up, the patient remained disease-free. By contrast, a right renal tumor was identified in the 74-year-old female patient during a routine examination. Radical right nephrectomy and lymph node dissection were performed, however, 10 months after surgery the patient succumbed due to wide-spread metastasis. The two cases reported in the present study not only represent excellent examples of the disease spectrum, but also act as a reminder of the possibility of detecting BDC in an early stage of disease. Therefore, the epidemiology of BDC has been discussed, and the aggressive growth pattern of BDC has been presented in terms of signs, symptoms and imaging examinations, including ultrasonography, computed tomography (CT), angiography and single photon emission CT, in the early stage of disease.

Progressive dysphasic dementia with bucco-facial apraxia: a case report.

A patient with progressive dementia, prominent non-fluent aphasia and signs of frontal lobe involvement, was evaluated by neuropsychological testing, magnetic resonance imaging (MRI) and high resolution single photon emission tomography (SPET). The presence of severe bucco-facial apraxia, associated with spared imitation of limb movements, correlated well with a marked reduction of cerebral perfusion in the left fronto-temporal cortex. This case emphasizes the usefulness of SPET as a valuable alternative to PET for the diagnosis of conditions, such as progressive neuropsychological syndromes, where a coupled reduction of metabolism and blood flow can be expected.

Therapy region monitoring based on PET using 478 keV single prompt gamma ray during BNCT: A Monte Carlo simulation study

We confirmed the feasibility of using our proposed system to extract two different kinds of functional images from a positron emission tomography (PET) module by using an insertable collimator during boron neutron capture therapy (BNCT). Coincidence events from a tumor region that included boron particles were identified by a PET scanner before BNCT; subsequently, the prompt gamma ray events from the same tumor region were collected after exposure to an external neutron beam through an insertable collimator on the PET detector. Five tumor regions that contained boron particles and were located in the water phantom and in the BNCT system with the PET module were simulated with Monte Carlo simulation code. The acquired images were quantitatively analyzed. Based on the receiver operating characteristic (ROC) curves in the five boron regions, A, B, C, D, and E, the PET and single-photon images were 10.2%, 11.7%, 8.2% (center region), 12.6%, and 10.5%, respectively. We were able to acquire simultaneously PET and single prompt photon images for tumor regions monitoring by using an insertable collimator without any additional isotopes.

Determination of optimal collimation parameters for a rotating slat collimator system: a system matrix method using ML-EM

Nowadays, Single Photon imaging has become an essential part of molecular imaging and nuclear medicine. Whether to establish a diagnosis or in the therapeutic monitoring, this modality presents performance that continues to improve. For over 50 years, several collimators have been proposed. Mainly governed by collimation parameters, the resolution-sensitivity trade-off is the factor determining the collimator the most suitable for an intended study. One alternative to the common approaches is the rotating slat collimator (RSC). In the present study, we are aiming at developing a preclinical system equipped with a RSC dedicated to mice and rats imaging, which requires both high sensitivity and spatial resolution. We investigated the resolution-sensitivity trade-offs obtained by varying different collimation parameters: (i) the slats height (H), and (ii) the gap between two consecutive slats (g), considering different intrinsic spatial resolutions. One system matrix was generated for each set of collimation parameters (H,g). Spatial resolutions, Signal-to-Noise Ratio (SNR) and sensitivity obtained for all the set of collimation parameters (H,g) were measured in the 2D projections reconstructed with ML-EM. According to our results, 20 mm high slats and a 1 mm gap were chosen as a good RSC candidate for a preclinical detection module. This collimator will ensure a sensitivity greater than 0.2% and a system spatial resolution below 1 mm, considering an intrinsic spatial resolution below 0.8 mm.

Low-noise reset technique of an asynchronous charge-pulse-detecting pixel for single-photon X-ray imaging

This paper presents a low-noise reset technique of an asynchronous charge-pulse-detecting pixel for single-photon X-ray imaging. The proposed slow-slope ramp (S2R) reset scheme provides a reset-noise-discharging loop circuit and effectively eliminates the residual noise charge stored on the sampling capacitor by extending the falling transition time of the reset signal. In addition, the presented S2R reset signal generation circuit accurately and effectively controls the optimum switching voltage and the falling transition time of the reset signal. The prototype detector chip was implemented by using a 130-nm complementary metal-oxide semiconductor (CMOS) process. With the quantitative analysis and the measurement results, we were able to verify that the reset noise was reduced exponentially, corresponding to the falling transition time of the reset signal. Based on the chip measurement results, the reset-noise level could be decreased by more than seven-fold by virtue of the proposed reset technique.

Quo Vadis: PET and Single-Photon Molecular Breast Imaging.

This supplement to The Journal of Nuclear Medicine on breast cancer imaging comprehensively addresses the current status of both PET and single-photon imaging of the breast and of localized and metastatic breast cancer. I was asked to introduce the supplement with a commentary that not only looks

Computational multi-depth single-photon imaging.

We present an imaging framework that is able to accurately reconstruct multiple depths at individual pixels from single-photon observations. Our active imaging method models the single-photon detection statistics from multiple reflectors within a pixel, and it also exploits the fact that a multi-depth profile at each pixel can be expressed as a sparse signal. We interpret the multi-depth reconstruction problem as a sparse deconvolution problem using single-photon observations, create a convex problem through discretization and relaxation, and use a modified iterative shrinkage-thresholding algorithm to efficiently solve for the optimal multi-depth solution. We experimentally demonstrate that the proposed framework is able to accurately reconstruct the depth features of an object that is behind a partially-reflecting scatterer and 4 m away from the imager with root mean-square error of 11 cm, using only 19 signal photon detections per pixel in the presence of moderate background light. In terms of root mean-square error, this is a factor of 4.2 improvement over the conventional method of Gaussian-mixture fitting for multi-depth recovery.

CO2BOLD assessment of moyamoya syndrome: Validation with single photon emission computed tomography and positron emission tomography imaging.

AIMTo compare the assessment of cerebrovascular reserve (CVR) using CO2BOLD magnetic resonance imaging (MRI) vs positron emission tomography (PET) and single photon emission computed tomography (SPECT) as reference standard.METHODSTen consecutive patients (8 women, mean age of 41 ± 26 years) with moyamoya syndrome underwent 14 pre-surgical evaluations for external-internal carotid artery bypass surgery. CVR was assessed using CO2BOLD and PET (4)/SPECT (11) with a maximum interval of 36 d, and evaluated by two experienced neuroradiologists.RESULTSThe inter-rater agreement was 0.81 for SPECT (excellent), 0.43 for PET (fair) and 0.7 for CO2BOLD (good). In 9/14 cases, there was a correspondence between CO2BOLD and PET/SPECT. In 4/14 cases, CVR was over-estimated in CO2BOLD, while in 1/14 case, CVR was underestimated in CO2BOLD. The sensitivity of CO2BOLD was 86% and a specificity of 43%.CONCLUSIONCO2BOLD can be used for pre-surgical assessment of CVR in patients with moyamoya syndrome and combines the advantages of absent irradiation, high availability of MRI and assessment of brain parenchyma, cerebral vessels and surrogate CVR in one stop.

Gender differences in the accuracy of stress 99mTc-sestamibi myocardial perfusion imaging

Introduction: Coronary artery disease (CAD) is a leading cause of death in both women and men worldwide. There is under-recognition and under-diagnosis of CAD as a cause of high mortality rates in women. There is paucity of data regarding comparison of sensitivity, specificity, and accuracy of myocardial perfusion imaging-single photon emission computed tomography (MPI-SPECT) study in women and men in Indian population. Hence, this study was carried out to compare the sensitivity, specificity, and accuracy of MPI in women and men in the Indian population. Material and Methods: This retrospective study included 275 patients, 49 women and 226 men. Only patients who had coronary angiography (CAG) done within 6 months of the stress 99mTc-sestamibi MPI-SPECT study were included in the study. Two arbitrary cut-off points on CAG, i.e., ≥50% and ≥70% were used for the determination of extent of CAD. Results: Considering CAG as the gold standard with ≥50% coronary stenosis as the cut-off criteria for significant stenosis, the overall sensitivity, specificity, and accuracy, respectively, of MPI- SPECT was 80%, 65%, and 72% in women and 82%, 70%, and 76% in men (P value not significant). Considering ≥70% coronary stenosis as the cut off criteria for significant stenosis, the overall sensitivity, specificity, and accuracy, respectively, of MPI-SPECT was 88%, 57%, and 66% in women and 87%, 59%, and 70% in men (P value not significant). No significant difference was found in the sensitivity, specificity, and accuracy of left anterior descending, left circumflex artery, and right coronary artery coronary vessels among women and men for both ≥50% and ≥70% coronary stenosis as the cut off criteria. Conclusion: 99mTc-sestamibi MPI-SPECT has comparable sensitivity, specificity, and accuracy for the detection of CAD in women as it does in men.

Hybrid imaging: clinical evidence, opportunities

Nowadays the hybrid imaging technologies which combine the modern equipments of radiology and nuclear medicine play an important role in both the translational research process and clinical diagnostics. Among the routine diagnostic imaging procedures positron emission tomography and single photon emission computed tomography combined with computed tomography or magnetic resonance imaging currently belong to the most advanced techniques allowing that functional and morphological images can be superimposed on each other in the same position. The hybrid imaging equipments provide useful information about the pathological processes in the body due to their high sensibility and resolution. Furthermore, with the help of these imaging modalities we can get acquainted with the biochemical and pathobiochemical processes that are essential for understanding and treating diseases, or getting acquainted with the behaviour of a new drug candidate. With the help of the clinical and preclinical non-invasive in vivo molecular imaging systems the drug developing process can be shortened and its costs can be reduced.

Assessment of inpatient multimodal cardiac imaging appropriateness at large academic medical centers.

BackgroundResponding to concerns regarding the growth of cardiac testing, the American College of Cardiology Foundation (ACCF) published Appropriate Use Criteria (AUC) for various cardiac imaging modalities. Single modality cardiac imaging appropriateness has been reported but there have been no studies assessing the appropriateness of multiple imaging modalities in an inpatient environment.MethodsA retrospective study of the appropriateness of cardiac tests ordered by the inpatient General Internal Medicine (GIM) and Cardiology services at three Canadian academic hospitals was conducted over two one-month periods. Cardiac tests characterized were transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), single-photon emission tomography myocardial perfusion imaging (SPECT), and diagnostic cardiac catheterization.ResultsOverall, 553 tests were assessed, of which 99.8 % were classifiable by AUC. 91 % of all studies were categorized as appropriate, 4 % may be appropriate and 5 % were rarely appropriate. There were high rates of appropriate use of all modalities by GIM and Cardiology throughout. Significantly more appropriate diagnostic catheterizations were ordered by Cardiology than GIM (93 % vs. 82 %, p = <0.01). Cardiology ordered more appropriate studies overall (94 % vs. 88 %, p = 0.03) but there was no difference in the rate of rarely appropriate studies (3 % vs. 6 %, p = 0.23).ConclusionThe ACCF AUC captured the vast majority of clinical scenarios for multiple cardiac imaging modalities in this multi-centered study on Cardiology and GIM inpatients in the acute care setting. The rate of appropriate ordering was high across all imaging modalities. We recommend further work towards improving appropriate utilization of cardiac imaging resources focus on the out-patient setting.

Small area 0.3 pJ/conv, 45 ps time‐to‐digital converter for arrays of silicon photomultiplier interfaces in 150 nm CMOS

A ring-oscillator-based time-to-digital converter (TDC) is presented which can achieve a figure-of-merit of 0.3 pJ/conv in a very small footprint of 0.0024 mm2. Thanks to the optimisation of the ring-oscillator and of the sub-cycle interpolation, a 45-ps LSB is obtained with only 0.95 mW of power consumption. The area and power characteristics make the TDC suitable for its use in repeated instances, such as in multiple silicon photomultipliers readout channels or single-photon imaging devices with time-correlated detection.

Multicentre analysis of incidental findings on low-resolution CT attenuation correction images: an extended study.

To review new incidental findings detected on low-resolution CT attenuation correction (CTAC) images acquired during single-photon emission CT-CT myocardial perfusion imaging as an extension to our initial study. CTAC images acquired as part of myocardial perfusion imaging performed using single-photon emission CT at four UK nuclear medicine centres were evaluated as part of a multicentre study. New incidental findings that were considered to be clinically significant were evaluated further. Positive-predictive value (PPV) was determined at the time of definitive diagnosis. Out of 3485 patients, 962 (28%) patients had a positive finding on the CTAC image, of which 824 (24%) were new findings. 84 (2.4%) patients had findings that were considered clinically significant at the time of the CTAC report and which had not been previously diagnosed. However, only 10 (0.29%) of these had findings that were confirmed as clinically significant, with the potential to be detrimental to patient outcome, after follow-up and definitive diagnosis. The overall PPV from all centres over the 2-year period was 12%. Each centre achieved what we considered to be low PPVs with no significant difference between the present and initial studies. The additional data from the combined studies show that, statistically, there is no significant difference between the PPVs from any of the centres. We conclude that routine reporting of CTAC images is not beneficial. This study combined with the previous study offers a unique evaluation of new clinically significant incidental findings on low-resolution CT images in an attempt to determine the benefit of reporting the CTAC images.

Development of a (99m)Tc-labeled lactam bridge-cyclized alpha-MSH derivative peptide as a possible single photon imaging agent for melanoma tumors.

Melanocortin-1 (MC1) receptor is an attractive melanoma-specific target which has been used for melanoma imaging and therapy. In this work, a new lactam bridge α-MSH analog was labeled with (99m)Tc via HYNIC and EDDA/tricine as coligands including gamma aminobutyric acid (GABA) as a three carbon chain spacer between HYNIC and the N-terminus of the cyclic peptide. Also, stability in human serum, receptor bound internalization, in vivo tumor uptake, and tissue biodistribution were thoroughly investigated. HYNIC-GABA-Nle-CycMSHhept was synthesized using a standard Fmoc strategy. Labeling was performed at 95 °C and analysis involved instant thin layer chromatography and high performance liquid chromatography methods. The receptor bound internalization rate was studied in MC1 receptor expressing B16/F10 cells. Biodistribution of radiopeptide was studied in nude mice bearing B16/F10 tumor. Labeling yield of >98 % (n = 3) was obtained corresponding to a specific activity of 81 MBq/nmol. Peptide conjugate showed efficient stability in the presence of human serum. The radioligand showed specific internalization into B16/F10 cells (12.45 ± 1.1 % at 4 h). In biodistribution studies, a receptor-specific uptake was observed in MC1 receptor-positive organs so that after 2 h the uptake in mouse tumor was 5.10 ± 0.08 % ID/g, while low accumulation in the kidney uptake was observed (4.58 ± 0.68 % ID/g at 2 h after injection). The obtained results show that the presented new designed labeled peptide conjugate may be a suitable candidate for diagnosis of malignant tumors.

Gold Nanocluster Embedded Albumin Nanoparticles for Two-Photon Imaging of Cancer Cells Accompanying Drug Delivery.

Gold nanoclusters in albumin nanoparticles (nanovehicles) are used for single-photon and two-photon imaging of cancer cells following the delivery of doxorubicin through the nanovehicle. NIR excitation and emission wavelengths in the biological window (650-900 nm) make the nanovehicle an ideal potential platform for imaging guided drug delivery.

Sentinel lymph node biopsy in oral and oropharyngeal squamous cell carcinoma: current status and unresolved challenges.

Because imaging with ultrasound, computed tomography, magnetic resonance imaging or positron emission tomography is unreliable for preoperative lymph node staging of early-stage oral and oropharyngeal squamous cell carcinoma (OSCC), elective neck dissection has been typically performed. The targeted sampling of sentinel lymph nodes (SLN) identified by lymphoscintigraphy and detected by gamma probe has become an effective alternative for the selection of patients for regional nodal resection. With careful consideration to technique, high SLN detection rates have been reported. Advanced techniques including intraoperative handheld gamma camera imaging and freehand single photon emission computed tomography (SPECT) are expected to increase surgical confidence in these procedures. This review gives an update on SLN biopsy in patients with OSCC including clinical standards and controversial aspects.

Putative Microcircuit-Level Substrates for Attention Are Disrupted in Mouse Models of Autism

BackgroundDeep layer excitatory circuits in the prefrontal cortex represent the strongest locus for genetic convergence in autism, but specific abnormalities within these circuits that mediate key features of autism, such as cognitive or attentional deficits, remain unknown. Attention normally increases the sensitivity of neural populations to incoming signals by decorrelating ongoing cortical circuit activity. Here, we investigated whether mechanisms underlying this phenomenon might be disrupted within deep layer prefrontal circuits in mouse models of autism. MethodsWe isolated deep layer prefrontal circuits in brain slices then used single-photon GCaMP imaging to record activity from many (50 to 100) neurons simultaneously to study patterns of spontaneous activity generated by these circuits under normal conditions and in two etiologically distinct models of autism: mice exposed to valproic acid in utero and Fmr1 knockout mice. ResultsWe found that modest doses of the cholinergic agonist carbachol normally decorrelate spontaneous activity generated by deep layer prefrontal networks. This effect was disrupted in both valproic acid-exposed and Fmr1 knockout mice but intact following other manipulations that did not model autism. ConclusionsOur results suggest that cholinergic modulation may contribute to attention by acting on local cortical microcircuits to decorrelate spontaneous activity. Furthermore, defects in this mechanism represent a microcircuit-level endophenotype that could link diverse genetic and developmental disruptions to attentional deficits in autism. Future studies could elucidate pathways leading from various etiologies to this circuit-level abnormality or use this abnormality itself as a target and identify novel therapeutic strategies that restore normal circuit function.

Usefulness of the Chang attenuation correction method with use of a CT-based μ map by FBP reconstruction in 201Tl SPECT-MPI

Attenuation correction (AC) on nuclear images of non-uniform domains is generally performed by a change of the computed tomography (CT) values to μ values, which are then inserted as components into the detection probability of iterative reconstruction techniques (OS-EM Iterative AC). We established an AC technique which uses a CT μ map based on the Chang AC. Our purpose in this study was to confirm the appropriateness of the Chang AC with the OS-EM and the FBP method (OS-EM Chang AC and FBP Chang AC) by evaluating the results obtained in a phantom and clinical study for (201)Tl single-photon emission-computed tomography-myocardial perfusion imaging (SPECT-MPI). Myocardial phantom study and retrospective clinical study were performed. Evaluations for image quality (uniformity and contrast) and image quantitative values [accurate left ventricular (LV) volume and radioactivity] were performed for both studies. FBP Chang AC showed good image uniformity and proper contrast in phantom and clinical study. Accurate LV volume and radioactivity in the myocardium were also obtained by the phantom study. On the other hand, the number of iterations influenced the image quality both in OS-EM Iterative AC and OS-EM Chang AC in the phantom study. Different numbers of iterations were necessary for obtaining good contrast ratio in each of the anterior and inferior wall, and accurate LV volume. The number of iterations influences the image quality and quantitative values on OS-EM Iterative Chang AC and OS-EM Chang AC images. In addition, it is difficult to set an appropriate number of iterations for the iterative reconstruction of these images in phantom and clinical studies. Therefore, FBP Chang AC is considered to be clinically useful.