Single-photon Emission Tomography Imaging Research Articles

Chromatographic separation of silver-111 from neutron-irradiated palladium target: toward direct labeling of radiotracers

BackgroundSilver-111 is a promising β−-emitting radioisotope with ideal characteristics for targeted radionuclide therapy and associated single photon emission tomography imaging. Its decay properties closely resemble the clinically established lutetium-177, making it an attractive candidate for therapeutic applications. In addition, the clinical value of silver-111 is further enhanced by the existence of the positron-emitting counterpart silver-103, thus imparting a truly theranostic potential to this element. A so-fitting matching pair could potentially overcome the current limitations associated with the forced use of chemically different isotopes as imaging surrogates of lutetium-177, leading to more accurate and efficient diagnosis and treatment. However, the use of silver-111-based radiopharmaceuticals in vivo has faced obstacles due to the challenges related to its production and radiochemical separation from the target material. To address these issues, this study aims to implement a chromatographic separation methodology for the purification of reactor-produced silver-111. The ultimate goal is to achieve a ready-to-use formulation for the direct radiolabeling of tumour-seeking biomolecules.ResultsA two-step sequence chromatographic process was validated for cold Ag-Pd separation and then translated to the radioactive counterpart. Silver-111 was produced via the 110Pd(n,γ)111Pd nuclear reaction on a natural palladium target and the subsequent β−-decay of palladium-111. Silver-111 was chemically separated from the metallic target via the implemented chromatographic process by using commercially available LN and TK200 resins. The effectiveness of the separations was assessed by inductively coupled plasma optical emission spectroscopy and γ-spectrometry, respectively, and the Ag+ retrieval was afforded in pure water. Recovery of silver-111 was > 90% with a radionuclidic purity > 99% and a separation factor of around 4.21·10−4.ConclusionsThe developed separation method was suitable to obtain silver-111 with high molar activity in a ready-to-use water-based formulation that can be directly employed for the labeling of radiotracers. By successfully establishing a robust and efficient production and purification method for silver-111, this research paves the way for its wider application in targeted radionuclide therapy and precision imaging.

Degradation Adaptability Assessment of Semisolid Powder Molded Mg-Zn-Mn Alloys for Orthopedic Applications.

Semisolid powder molding was used to prepare the medical Mg-6Zn alloy; in order to further improve its degradation adaptability, 0.5 and 1 wt % Mn were added. Then, the effect of the forming temperature (540, 560, 580, and 600 °C) on the in vitro degradation behavior of the prepared Mg-6Zn-xMn (x = 0.5, 1 wt %) was analyzed, and the optimized alloy was obtained. Finally, the biocompatibility and in vivo degradation performance of the optimized and Mn-free alloys were evaluated. Importantly, single-photon emission tomographic imaging (SPECT/CT) was first applied to monitor the in vivo degradation process. The results show that the corrosion mechanism of the Mn-free alloy is microgalvanic corrosion control with corrosive pitting. After adding Mn, the in vitro degradation rate decreases by half (0.17 ± 0.01 mm/year) as the forming temperature increases to 600 °C, and Mg-6Zn-1Mn prepared at 600 °C is the optimized alloy. Mn addition improves the corrosion product film protection and discontinuous secondary phases, and thus, the corrosion mechanism is changed to corrosive pitting control. Additionally, semisolid powder molding is an easy method to prepare alloys with low average pore interconnectivity (<10%), which is helpful for slowing down the degradation rate. The Mn-containing alloy has better biocompatibility, with a cytotoxicity of grade 0-1, due to its lower degradation rate. The in vivo corrosion rate of the Mn-free alloy is 0.19 mm/year after 28 days of implantation, which was precisely detected by SPECT/CT in real-time. The long-term in vivo degradation adaptability of Mn-free and Mn-containing alloys was not correctly presented, which may be due to the unreasonable bone defect model causing implant displacement. However, both of these alloys cause no obvious inflammation and show good healing. In summary, semisolid powder molding is a potentially promising technique to prepare medical Mg alloys, and nuclear imaging is an effective in vivo degradation evaluation method.

Compressed sensing reconstruction shortens the acquisition time for myocardial perfusion imaging: a simulation study.

Compressed sensing (CS) has been used to improve image quality in single-photon emission tomography (SPECT) imaging. However, the effects of CS on image quality parameters in myocardial perfusion imaging (MPI) have not been investigated in detail. This preliminary study aimed to compare the performance of CS-iterative reconstruction (CS-IR) with filtered back-projection (FBP) and maximum likelihood expectation maximization (ML-EM) on their ability to reduce the acquisition time of MPI. A digital phantom that mimicked the left ventricular myocardium was created. Projection images with 120 and 30 directions (360°), and with 60 and 15 directions (180°) were generated. The SPECT images were reconstructed using FBP, ML-EM, and CS-IR. The coefficient of variation (CV) for the uniformity of myocardial accumulation, septal wall thickness, and contrast ratio (Contrast) of the defect/normal lateral wall were calculated for evaluation. The simulation was performed ten times. The CV of CS-IR was lower than that of FBP and ML-EM in both 360° and 180° acquisitions. The septal wall thickness of CS-IR at the 360° acquisition was inferior to that of ML-EM, with a difference of 2.5mm. Contrast did not differ between ML-EM and CS-IR for the 360° and 180° acquisitions. The CV for the quarter-acquisition time in CS-IR was lower than that for the full-acquisition time in the other reconstruction methods. CS-IR has the potential to reduce the acquisition time of MPI.

Outcomes following transarterial radioembolization with 90Y and nanoparticles loaded resin microspheres

90Y bremsstrahlung Single-Photon Emission Tomography (SPECT) imaging is employed to check the possibility of extrahepatic uptake and the quantification of delivered dose in Transarterial Radioembolization (TARE). 90Y bremsstrahlung SPECT imaging is challenging due to the nature of bremsstrahlung photons. We reported a Monte Carlo study using the resin microspheres loaded with 90Y and Nanoparticles (NPs) in the TARE. By injection of Bismuth (Bi) and Europium (Eu) NPs into the resin microspheres, the sensitivity and the contrast to noise ratio increased for the bremsstrahlung planar images. The highest signal to background ratio was observed in the characteristic X-ray planar images taken with the energy window at the Kα1 ± 10 keV when Eu NPs were incorporated into the microsphere. The dose enhancement ratio decreased dramatically at NP concentrations >2.4 M. Incorporating NPs into the resin microspheres improves the quality of post-treatment images and establishes a standardized imaging protocol for post-treatment imaging by characteristic X-rays.

A new approach to overcome the inconsistency between SPECT and the anatomical map in maximum A-posterior expectation-maximization reconstruction algorithm

Noise reduction while preserving spatial resolution is one of the most important challenges in the reconstructing of emission tomography images. One of the resolving methods is the Bowsher maximum a-posteriori expectation-maximization reconstruction (MAPEM) algorithm. This method considers a binary selection of the neighbors of each voxel based on the prior anatomical values to use in the regularization function. This method is particularly susceptible to imposing the wrong data into the reconstructed image due to the spatial or functional inconsistencies between the anatomical image and the actual activity distribution. Because of the poor spatial resolution of single-photon emission tomography (SPECT) images and the different nature of emission and anatomical imaging, there is not enough certainty of inconsistency with anatomical images. Therefore, we proposed a new weighted Bowsher method that can overcome this weakness while the image quality indexes, especially the spatial resolution, are almost preserved. In the proposed method, each of the neighbors of a specific voxel takes a constant weight depending on the order of its value and independent of its intensity quantity. The proposed method was evaluated using some different physical phantoms and a patient scan. The results show that the proposed method has superiority in the presence of inconsistency; moreover, the proposed method gives nearly similar results to the regular Bowsher MAPEM in case of consistency. In conclusion, we show that using a suitable constant weighting factor in Bowsher MAPEM, one can operatively reduce the image noise while preserving the image quality parameters where the emission tomography images are either consistent or inconsistent with the prior anatomical map.

One-step synthesis of a radioiodinated anti-microRNA-21 oligonucleotide for theranostics in prostate tumor xenografts

Anti-miRNA oligonucleotide (AMO) has been used most widely to inhibit miRNA for loss-of-function studies and function as therapeutic agents. Iodine-131 (131I) radiolabeled AMO may have multiple functions for specific imaging, genetic inhibition, and radiotherapy. This study is to prepare a radioiodinated anti-miRNA-21 AMO by one-step synthesis for preliminary imaging in tumor xenografts and in vitro radiotherapy. A tyrosine was conjugated at the 3’ end of AMO via a C6 linker for labeling with 131I. After the molecular mass of AMO was confirmed by mass spectrometry, AMO was labeled with 131I by the chloramine-T method with high labeling yield (95.5% ± 3.1%). By gel electrophoresis, the radioactive distribution of 131I-AMO was located exactly where was AMO, verifying the successful radiolabeling. 131I-AMO presented high stability during 24 h of incubation in fresh human serum. The cellular uptake of 131I or FAM-labeled AMO in DU145 was significantly higher than that in PC-3 cells. After i.v. administration in mice, single-photon emission tomography (SPECT) imaging showed that increased 131I-AMO was found in DU145 tumor from 4 h to 24 h gradually. H&E staining of major organs validated the biocompatibility of 131I-AMO in vivo. Furthermore, the ability of 131I-AMO to inhibit cell growth is superior to that of 131I, along with stronger apoptosis in DU145 cells than in PC-3 cells. Therefore, AMO can be labeled with 131I via one-step synthesis after tyrosine conjugation in this study. Its high labeling yield, stability, inhibitory effect, and tumor distribution provide the potential value in the targeted theranostic role.

Clinical Evaluation of Nuclear Imaging Agents in Breast Cancer.

Simple SummaryBreast cancer is currently the most common type of diagnosed cancer worldwide. Noninvasive imaging of therapeutic targets or biomarkers for breast cancer has the potential to contribute to precision medicine, where targeted therapy is needed. Positron emission tomography (PET) or single-photon emission tomography (SPECT) imaging with radiolabeled probes has the potential to play an important role in the molecular profiling of therapeutic targets in vivo for the selection of patients who are likely to respond to corresponding targeted therapy. This review covers recent clinical investigations with noninvasive imaging agents in breast cancer. We reviewed 17 clinical studies on PET or SPECT agents that target 10 receptors in breast cancer.Precision medicine is the customization of therapy for specific groups of patients using genetic or molecular profiling. Noninvasive imaging is one strategy for molecular profiling and is the focus of this review. The combination of imaging and therapy for precision medicine gave rise to the field of theranostics. In breast cancer, the detection and quantification of therapeutic targets can help assess their heterogeneity, especially in metastatic disease, and may help guide clinical decisions for targeted treatments. Positron emission tomography (PET) or single-photon emission tomography (SPECT) imaging has the potential to play an important role in the molecular profiling of therapeutic targets in vivo for the selection of patients who are likely to respond to corresponding targeted therapy. In this review, we discuss the state-of-the-art nuclear imaging agents in clinical research for breast cancer. We reviewed 17 clinical studies on PET or SPECT agents that target 10 different receptors in breast cancer. We also discuss the limitations of the study designs and of the imaging agents in these studies. Finally, we offer our perspective on which imaging agents have the highest potential to be used in clinical practice in the future.

[Analysis of brain perfusion single-photon emission tomography images using an easy Zscore imaging system for early diagnosis of Alzheimer's disease].

To analyze single-photon emission tomography (SPECT) images of cerebral blood flow perfusion using an easy Z-score imaging system (eZIS) and explore the value of SPECT and eZIS in early diagnosis of Alzheimer's disease (AD). We retrospectively analyzed the clinical data of 71 subjects undergoing brain perfusion SPECT examination in our department from September, 2018 to September, 2020 and identified 31 eligible subjects for this study. Among these subjects, according to the NIA-AA criteria (2011 edition), 12 were diagnosed with mild cognitive impairment due to AD (MCI) and 11 with AD dementia stage (AD); 8 elderly subjects were healthy without cognitive impairment (NC). All these subjects underwent brain perfusion SPECT, and eZIS-assisted analysis was used to obtain the index values (severity, range and ratio). The differences in the severity, extent and ratio among the 3 groups were compared, and the diagnostic efficacy of single and joint analysis of the 3 indexes for early AD was analyzed. There was no significant difference in gender, age and education level among the 3 groups (P>0.05). Compared with those in NC group, the Mini Mental State Examination Scale (MMSE) scores were significantly lowered in AD group and MCI group; the MMSE score was significantly lower in AD group than in MCI group (P < 0.05). The patients with AD had significantly greater disease severity and extent than those with MCI group; the severity, range and ratio in both AD group and MCI group were significantly higher than those of NC group, but the ratio did not differ significantly between AD group and MCI group (P>0.05). In single index analysis, severity had the highest diagnostic performance (AUC=0.911) and sensitivity (87.0%); the diagnostic performance and sensitivity of joint analysis were better than those of single analysis, and joint analysis of range and ratio showed high diagnostic performance (AUC=0.948) and sensitivity (87.0%). The analysis of brain perfusion SPECT using an eZIS program can be useful for early diagnosis of AD.

New advances in pre-clinical diagnostic imaging perspectives of functionalized upconversion nanoparticle-based nanomedicine

• Recent advances on surface functionalized upconversion nanoparticles synthesis, functionalization, and toxicity concerns are enlightened. • Targeted delivery of nanoconstructs and developments in biomedical, fluorescence, MR CT, X-ray, PET, and SPECT are highlighted. • Current challenges and imaging development of nanoconstructs are discussed. • Luminescent nanomedicine at advanced stage clinical settings for diagnosis and Therapeutics is emphasized. In widespread progress of nanoparticles (NPs) based biomedical applications particularly in leukemia cancer treatment. Upconversion nanoparticles (UCNPs) demonstrated outstanding optical, physicochemical properties and high penetration depth, free of autofluorescence, minimum toxicity inspired the researchers to improve the high-quality specific targeting UCNPs. High crystallinity and weak hydrophilicity are some drawbacks that produced significant side effects and poor therapeutic effectiveness during the imaging process. In cutting-edge materials intended for in vivo /vitro biomedical applications, UC is known to be a basic part and advantage from their extraordinary benefits of Stokes UC luminescence (L) properties. During in vivo applications, the NIR light excitation takes into consideration an expansive infiltration profundity in bio-tissues. This examination talks about current advancements in the enhancement and functionalization of biomedical imaging/and in vivo treatment of UC nanomaterials. We at that point address the synthetic methodologies used to make these UCNPs biocompatible and aqueous-dissolvable for UCNP surface functionalization, and further delineate some agent instances of the utilization of UCNPs for different in vivo /vitro biomedical imagingbiomedical imaging techniques including UC luminescence imaging (UCL), magnetic resonance imaging (MRI), X-ray computed tomography(CT) imaging, positron emission tomography(PET) imaging, and single-photon emission tomography(SPECT) imaging. The requirement for precise nanotoxicology information for objective plans of UCNP materials, their exterior science-engineering in more secure/safer biomedical applications, is discussed in the points of view. In this review, we would like to discuss the various significant factors to enhance the quality and quantum efficiency of the UCNPs, through surface functionalization and further their implementation in various bio-imaging techniques. The future challenges and guidelines were discussed to get the expected results in the current imaging techniques. First, biodistribution and clearance should be considered when they mediate the fate of a contrast agent in the bloodstream, such as how long a contrast agent reaches the highest signal-to-background ratio following intravenous injection and how long the signal lasts.

Improved Performance of a Multipinhole SPECT for DAT Imaging by Increasing Number of Pinholes at the Expense of Increased Multiplexing.

SPECT imaging of dopamine transporters (DAT) in the brain is a widely utilized study to improve the diagnosis of Parkinsonian syndromes, where conventional (parallel-hole and fan-beam) collimators on dual-head scanners are commonly employed. We have designed a multi-pinhole (MPH) collimator to improve the performance of DAT imaging. The MPH collimator focuses on the striatum and hence offers a better trade-off for sensitivity and spatial resolution than the conventional collimators within this clinically most relevant region for DAT imaging. Our original MPH design consisted of 9 pinholes with a background-to-striatal (Bkg/Str) projection multiplexing of 1% only. In this simulation study, we investigated whether further improvements in the performance of MPH imaging could be obtained by increasing the number of pinholes, hence by enhancing the sensitivity and sampling, despite the ambiguity in reconstructing images due to increased multiplexing. We performed analytic simulations of the MPH configurations with 9, 13, and 16 pinholes (aperture diameters: 4-6mm) using a digital phantom modeling DAT imaging. Our quantitative analyses indicated that using 13 (Bkg/Str: 12%) and 16 (Bkg/Str: 22%) pinholes provided better performance than the original 9-pinhole configuration for the acquisition with 2 or 4 angular views, but a similar performance with 8 and 16 views.

Feasibility of CT quantification of intratumoural 166Ho-microspheres

BackgroundMicrospheres loaded with radioactive 166Ho (166Ho-MS) are novel particles for radioembolisation and intratumoural treatment. Because of the limited penetration of β radiation, quantitative imaging of microsphere distribution is crucial for optimal intratumoural treatment. Computed tomography (CT) may provide high-resolution and fast imaging of the distribution of these microspheres, with lower costs and widespread availability in comparison with current standard single-photon emission tomography (SPECT) and magnetic resonance imaging. This phantom study investigated the feasibility of CT quantification of 166Ho-MS.MethodsCT quantification was performed on a phantom with various concentrations of HoCl and Ho-MS to investigate the CT sensitivity and calibrate the CT recovery. 166Ho-MS were injected into ex vivo tissues, in VX-2 cancer-bearing rabbits, and in patients with head-neck cancer, to demonstrate sensitivity and clinical visibility. The amount of Ho-MS was determined by CT scanning, using a density-based threshold method and compared with a validated 166Ho SPECT quantification method.ResultsIn the phantom, a near perfect linearity (least squares R2 > 0.99) between HU values and concentration of 166Ho was found. Ex vivo tissue experiments showed an excellent correlation (r = 0.99, p < 0.01) between the dose calibrator, SPECT, and CT imaging. CT recovery was on average 86.4% ex vivo, 76.0% in rabbits, and 99.1% in humans.ConclusionThis study showed that CT-based quantification of Ho microspheres is feasible and is a high-resolution alternative to SPECT-based determination of their local distribution.

Preclinical investigation of potential use of thymidine phosphorylase-targeting tracer for diagnosis of nonalcoholic steatohepatitis

IntroductionAlthough liver biopsy is the gold standard for the diagnosis of nonalcoholic steatohepatitis (NASH), it has several problems including high invasiveness and sampling errors. Therefore, the development of alternative methods to overcome these disadvantages is strongly required. In this study, we evaluated the potential use of our tracer targeting thymidine phosphorylase (TYMP), 5-[123I]iodo-6-[(2-iminoimidazolidinyl)methyl]uracil ([123I]IIMU) for the diagnosis of NASH. MethodsThe mice used as the NASH model (hereafter, NASH mice) were prepared by feeding a methionine- and choline-deficient diet for 4 weeks. A control group was similarly given a control diet. The expression levels of the TYMP gene and protein in the liver were examined by real-time reverse-transcription polymerase chain reaction and western blot analyses. The localizations of [125I]IIMU and the TYMP protein in the liver were examined by autoradiography and immunohistochemical staining, respectively. Finally, the mice were injected with [123I]IIMU and single-photon emission tomography (SPECT) imaging was conducted. ResultsThe hepatic expression levels of TYMP were significantly lower in the NASH mice than in the control mice at both mRNA and protein levels, suggesting that a decrease in TYMP level could be an indicator of NASH. [125I]IIMU was uniformly distributed in the liver of the control mice, whereas it showed a patchy distribution in that of the NASH mice. The localization of [125I]IIMU was visually consistent with that of the TYMP protein in the liver of the control and NASH mice. SPECT analysis indicated that the hepatic accumulation of [123I]IIMU in the NASH mice was significantly lower than that in the control mice [SUV (g/ml): 4.14 ± 0.87 (Control) vs 2.31 ± 0.29 (NASH)]. Conclusions[123I]IIMU may provide a noninvasive means for imaging TYMP expression in the liver and may be applicable to the diagnosis of NASH.

Deep-learning-based imaging-classification\xa0identified cingulate island sign in dementia with Lewy bodies

The differentiation of dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) using brain perfusion single photon emission tomography is important but is challenging because these conditions exhibit typical features. The cingulate island sign (CIS) is the most recently identified specific feature of DLB for a differential diagnosis. The current study aimed to examine the usefulness of deep-learning-based imaging classification for the diagnoses of DLB and AD. Furthermore, we investigated whether CIS was emphasized by a deep convolutional neural network (CNN) during differentiation. Brain perfusion single photon emission tomography images from 80 patients, each with DLB and AD, and 80 individuals with normal cognition (NL) were used for training and 20 each for final testing. The CNN was trained on brain surface perfusion images. Gradient-weighted class activation mapping (Grad-CAM) was applied to the CNN to visualize the features that was emphasized by the trained CNN. The binary classifications between DLB and NL, DLB and AD, and AD and NL were 93.1%, 89.3%, and 92.4% accurate, respectively. The CIS ratios closely correlated with the output scores before softmax for DLB–AD discrimination (DLB/AD scores). The Grad-CAM highlighted CIS in the DLB discrimination. Visualization of learning process by guided Grad-CAM revealed that CIS became more focused by the CNN as the training progressed. The DLB/AD score was significantly associated with the three core features of DLB. Deep-learning-based imaging classification was useful for an objective and accurate differentiation of DLB from AD and for predicting clinical features of DLB. The CIS was identified as a specific feature during DLB classification. The visualization of specific features and learning processes could be critical in deep learning to discover new imaging features.

Relative Target Affinities of T-Cell-Dependent Bispecific Antibodies Determine Biodistribution in a Solid Tumor Mouse Model.

Anti-HER2/CD3, a T-cell-dependent bispecific antibody (TDB) construct, induces T-cell-mediated cell death in cancer cells expressing HER2 by cross-linking tumor HER2 with CD3 on cytotoxic T cells, thereby creating a functional cytolytic synapse. TDB design is a very challenging process that requires consideration of multiple parameters. Although therapeutic antibody design strategy is commonly driven by striving for the highest attainable antigen-binding affinity, little is known about how the affinity of each TDB arm can affect the targeting ability of the other arm and the consequent distribution and efficacy. To our knowledge, no distribution studies have been published using preclinical models wherein the T-cell-targeting arm of the TDB is actively bound to T cells. We used a combined approach involving radiochemistry, invasive biodistribution, and noninvasive single-photon emission tomographic (SPECT) imaging to measure TDB distribution and catabolism in transgenic mice with human CD3ε expression on T cells. Using CD3 affinity variants, we assessed the impact of CD3 affinity on short-term pharmacokinetics, tissue distribution, and cellular uptake. Our experimental approach determined the relative effects of (i) CD3 targeting to normal tissues, (ii) HER2 targeting to HER2-expressing tumors, and (iii) relative HER2/CD3 affinity, all as critical drivers for TDB distribution. We observed a strong correlation between CD3 affinity and distribution to T-cell-rich tissues, with higher CD3 affinity reducing systemic exposure and shifting TDB distribution away from tumor to T-cell-containing tissues. These observations have important implications for clinical translation of bispecific antibodies for cancer immunotherapy. Mol Cancer Ther; 17(4); 776-85. ©2018 AACR.

Single-photon emission tomography imaging in patients with Lyme disease treated with human embryonic stem cells.

Aim The purpose of this study was to evaluate the longitudinal changes in brain perfusion in patients with Lyme disease treated with human embryonic stem cells. Material and methods The study included 59 (age range 41.68 ± 16.37 years) patients with Lyme disease whose single-photon emission tomography imaging was performed before and after the human embryonic stem cell therapy. Technetium-hexa methyl propylene aminoxime single-photon emission tomography imaging was used to assess the hypoperfused lesions/regions in the brain prior to the therapy, as well as the improvement in perfusion after human embryonic stem cell treatment. Results After receiving human embryonic stem cell therapy, single-photon emission tomography imaging reflects a significant (>60%) improvement in 43 patients along with moderate (30-60%) and mild (<30%) improvement in 12 and four patients, respectively. The cerebral perfusion flow improved and the degree of hypoperfusion in the other regions significantly decreased after the human embryonic stem cell therapy. Interpretation of single-photon emission tomography imaging of brain images (before and after therapy) clearly presented the changes in color at various brain regions which represent the improvements in patients. Conclusion Single-photon emission tomography imaging could be used as a potential diagnostic tool to assess the response of Lyme disease patients to human embryonic stem cell therapy.

Combining high-sensitivity cardiac troponin and B-type natriuretic peptide in the detection of inducible myocardial ischemia

BackgroundSingle biomarker approaches provide only moderate accuracy in the non-invasive detection of exercise-induced myocardial ischemia. We therefore assessed the combination of the two most promising single biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP). MethodsConsecutive patients with suspected myocardial ischemia referred to stress myocardial perfusion single-photon emission tomography imaging (MPI) were enrolled. Clinical judgment (CJ) of the treating cardiologist regarding myocardial ischemia, quantified using a visual analogue scale, and blood concentrations of hs-cTnI and BNP were determined before and after stress. The presence of myocardial ischemia was adjudicated by independent cardiologists using MPI, blinded to biomarker measurements. Death and acute myocardial infarction (AMI) during follow-up were the prognostic endpoints. ResultsAmong 1142 consecutive patients inducible myocardial ischemia was found in 456 (40%) of all patients. For the detection of inducible myocardial ischemia, CJ before exercise stress testing (CJb) showed an area under the receiver-operating-characteristics curve (AUC) of 0.66 (95%CI 0.63–0.69), hs-cTnI 0.70 (95%CI 0.67–0.73, p=0.07 vs CJb), and BNP 0.66 (95%CI 0.62–0.69, p=0.98). The use of a dual-biomarker strategy combining hs-cTnI and BNP with CJb did not provide a significant advantage over the combination of hs-cTnI alone and CJb (AUC 0.74, 95%CI 0.72–0.77 vs AUC 0.74, 95%CI 0.71–0.77, p=0.16). Hs-cTnI showed good prognostic value for AMI (HR 1.6, 95%CI 1.3–1.9), and BNP for death (HR 1.6, 95%CI 1.3–2.1). ConclusionA dual-biomarker strategy combing BNP and hs-cTnI does not further increase diagnostic accuracy on top of clinical judgment and hs-cTnI alone. Summary and highlightsWe included 1142 consecutive patients with suspected inducible ischemia, and evaluated the added value of the biomarkers high-sensitivity cardiac troponin (hs-cTn) and B-type natriuretic peptide (BNP), alone and in combination, on top of clinical judgment. Clinical trial registrationBiochemical and Electrocardiographic Signatures in the Detection of Exercise-induced Myocardial Ischemia (BASEL VIII), NCT01838148, https://clinicaltrials.gov/ct2/show/NCT01838148

CT and SPECT image fusion using external fiducial markers for detection of the sentinel lymph nodes in breast cancer

Object: Hybrid single-photon emission computed tomography/computed tomography, which is recently developed, is useful for the sentinel node (SN) mapping in patients with breast cancer. However, this expensive new technology is only available at limited hospitals. The purpose of this study was to assess the feasibility of software-based computed tomography (CT) and single-photon emission tomography (SPECT) image fusion using external fiducial markers for visualization of SNs in breast cancer.Methods: Preoperative lymphoscintigraphy using 99mTc-phytate colloid was performed in 70 consecutive patients (mean age, 55.3 ± 11.8). Continually, SPECT and low-dose chest CT were performed using an 241Am-containing button as an external fiducial marker attached to the skin surface of the patient’s chest wall. The acquired SPECT and CT images were rescaled, interpolated, reformatted, and registered point-by-point on a workstation.Results: SPECT detected SN sites, including axillar (n = 96) and internal mammary lesions (n = 7). On fused images, precise overlap of hot spots shown at the corresponding lymph nodes on CT images was achieved in all but 2 cases. In cases with axillar lesions, rendering the fused images into 3D volumes with accentuation of the pectoralis minor muscle was helpful for diagnosis of SN locations in level II (n = 10). After surgery, all nodes were depicted as “hot nodes” on fused images, and 14 metastatic nodes were confirmed by histological examination.Conclusions: External fiducial-based coregistration of SPECT lymphoscintigraphic and CT images depicted the precise location of SN drainage and may provide useful information for preoperative planning, without the need for hybrid SPECT/CT.

CT and SPECT image fusion using external fiducial markers for detection of the sentinel lymph nodes in breast cancer

Object: Hybrid single-photon emission computed tomography/computed tomography, which is recently developed, is useful for the sentinel node (SN) mapping in patients with breast cancer. However, this expensive new technology is only available at limited hospitals. The purpose of this study was to assess the feasibility of software-based computed tomography (CT) and single-photon emission tomography (SPECT) image fusion using external fiducial markers for visualization of SNs in breast cancer.Methods: Preoperative lymphoscintigraphy using 99mTc-phytate colloid was performed in 70 consecutive patients (mean age, 55.3 ± 11.8). Continually, SPECT and low-dose chest CT were performed using an 241Am-containing button as an external fiducial marker attached to the skin surface of the patient’s chest wall. The acquired SPECT and CT images were rescaled, interpolated, reformatted, and registered point-by-point on a workstation.Results: SPECT detected SN sites, including axillar (n = 96) and internal mammary lesions (n = 7). On fused images, precise overlap of hot spots shown at the corresponding lymph nodes on CT images was achieved in all but 2 cases. In cases with axillar lesions, rendering the fused images into 3D volumes with accentuation of the pectoralis minor muscle was helpful for diagnosis of SN locations in level II (n = 10). After surgery, all nodes were depicted as “hot nodes” on fused images, and 14 metastatic nodes were confirmed by histological examination.Conclusions: External fiducial-based coregistration of SPECT lymphoscintigraphic and CT images depicted the precise location of SN drainage and may provide useful information for preoperative planning, without the need for hybrid SPECT/CT.

A Novel Modality for Functional Imaging in Acute Intervertebral Disk Herniation via Tracking Leukocyte Infiltration.

Inflammation plays a key role in the progression of intervertebral disk (IVD) herniation and associated low back pain. However, real-time spatial diagnosis of inflammation associated with acute disk herniation has not been investigated. We sought to detect local neutrophil and macrophage infiltration near disk herniation via the formyl peptide receptor 1 (FPR1)-mediated molecular imaging in a disk puncture mouse model to elucidate pathophysiological process of disk herniation. Disk herniation was induced in mouse with an established needle puncture procedure. Degenerative change of disk and infiltration of neutrophils and macrophages were detected with Safranin-O, hematoxylin and eosin (H&E), and immunohistochemical staining after injury. FPR1-specific imaging probes cFLFLF-PEG-Cy7 and [99mTc]HYNIC-PEG-cFLFLF were administered systemically to sham and disk injury mice. Leukocyte infiltration was tracked by in vivo near-infrared fluorescence (NIRF) and single-photon emission tomography (SPECT) imaging. The peptide-receptor binding specificity was further investigated with FPR1-/- mice via ex vivo NIRF scan and in vitro binding assays. Safranin-O staining exhibited disorganized disk structure and loss of proteoglycan after puncture. Massive inflammatory cells were observed in the anterior region of punctured annulus in the injury group. The majority of neutrophils were detected at 1 through 3days, while infiltration of macrophages appeared the most at 7days after injury. NIRF and SPECT images revealed preferential accumulation of cFLFLF probes in herniation site in wild-type mice but not in FPR1-/- mice. Binding of the cFLFLF peptide to FPR1 was also observed in RAW 267.4 cells and macrophages isolated from wild-type mice, whereas much less signal was observed in macrophages from FPR1-/- mice. The presence of macrophage infiltration was also detected in human-herniated disk samples by immunohistochemistry. For the first time, leukocyte infiltration around acute disk herniation site was detected directly and non-invasively in a timely fashion using FPR1-targeted molecular imaging modalities. Such functional imaging of disk herniation via infiltrated leukocytes would advance the understanding of etiology and facilitate drug delivery and treatment monitoring of disk herniation.

Prognostic value of extracardiac incidental findings on attenuation correction cardiac computed tomography

BackgroundAttenuation corrected computed tomography (CTAC) is often performed to improve the specificity of single-photon emission tomography imaging. Extracardiac incidental findings are frequently observed. It is unclear whether these findings have any prognostic value. MethodsConsecutive patients (n = 1139) at a tertiary care center were retrospectively evaluated for incidental findings on CTAC. Clinically significant incidental findings were defined as findings warranting physician follow-up. Information regarding subsequent resource utilization was obtained by chart review. Cox proportional hazard model adjusted for demographic and clinical variables was used to evaluate association of these incidental findings with all-cause and cancer-specific mortality. ResultsA total of 135 (12%) patients with incidental findings were identified, 83 of whom (68%) were newly diagnosed. Lung nodules were the most common finding, present in 92 (68%) patients. Over a median follow-up of 468 days, incidental findings were not significantly associated with increased risk of all-cause mortality (HR 1.34; 95% CI 0.77-2.33, P = 0.29) but was significantly associated with cancer-specific mortality (HR 3.21; 95% CI 1.26-8.14, P = 0.01). This association remained statistically significant when the analysis was limited to newly diagnosed incidental findings. Among patients with incidental findings, follow-up radiographic studies were conducted in 87%, and invasive procedures performed in 32%. Physician office-based follow-up of these findings occurred in 42% of patients and incidental finding-related hospitalization occurred in 14%. ConclusionsThis study shows that incidental findings are common and were associated with all-cause and cancer-specific mortality but only the later remained statistically significant after multivariable adjustment.