Molecular Beacons Illuminate Subcellular Events

Current state-of-the-art care ensures that most patients with myocardial infarction (MI) survive the acute ischemic event. There is strong evidence that timely reperfusion therapy limits the loss of myocardium, preserves cardiac function, and improves survival. Conversely, delayed or insufficient tissue reperfusion results in prolonged ischemia and myocyte death. Necrotic cell death initiates the wound-healing process that parallels the response of the body to other sterile injuries. Unlike other injuries, for instance, a bone fracture for which a plaster cast can reduce tissue movement during repair, wound healing after MI can be greatly affected by cardiac motion and wall stress. The efficacy of healing is important, and suboptimal healing leads to weakened resistance to mechanical forces, which in turn results in infarct expansion, adverse remodeling, and ultimately, heart failure. Although angiotensin-converting enzyme inhibitors and β-blockers help reduce adverse remodeling, the desire to regenerate functioning heart muscle has motivated considerable interest in stem cell research, and recent discoveries on myocyte turnover are fueling the hope that one day “regrown” myocytes can replace the lost contractile units. Because there will be no plaster …

Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are functional nuclear medicine techniques which allow for accurate non-invasive in vivo measurements of a wide range of regional tissue functions in man. Brain functional imaging with SPECT and PET is based on the recording of the distribution of administered radionuclides in three dimensions, thus producing maps of brain biochemical and physiological processes. SPECT and PET techniques are able to image brain perfusion and metabolism, as well as various neurotransmission or other cellular processes using specific radioligands which mark in vivo receptors, transporters or enzymes. Brain SPECT and PET imaging or molecular imaging -, has been applied to the study of Alzheimer’s disease (AD) for over two decades. These functional neuroimaging approaches have the capability of identifying subtle pathophysiologic changes in the brain before structural changes are present (Xu et al., 2000). Therefore they possess greater potential for accurate and early diagnosis, monitoring disease progression, and better treatment followup. Furthermore, the application of SPECT and PET techniques to the study of AD has led to increased understanding of the underlying pathology and the disease processes and improved the differential diagnosis from other neurodegenerative causes of dementia.

A systematic review of molecular imaging (PET and SPECT) in autism spectrum disorder: Current state and future research opportunities

CLINICAL PERFORMANCE OF RB82 MYOCARDIAL PERFUSION PET AND TC-99M SPECT IN PATIENTS WITH EXTREME OBESITY (BMI ≥ 40)

The imaging of molecular events in the complex physiological interplay between organelles, cells, tissues, and organs in the whole organism is now more practical through the use of small-animal imaging technologies. Radionuclide based molecular imaging using single photon emission computed tomography (SPECT) and positron emission tomography (PET) scanners have been used for imaging intracellular enzymes, receptors, transporters, reporter gene expression, and cell trafficking in small animals such as mice and rats. Sensitive cooled charge-coupled device (CCD) cameras which detect emitted light from fluorescent and bioluminescent probes within an organism have been useful in imaging pathologic changes in diseases such as cancer and infectious disease in small-animal models. Each molecular imaging modality has differing strengths and weaknesses. However, the ability to generate molecular reporter strategies that can be applied in multiple detection systems will likely provide more robust imaging data sets than from any single modality. The ultimate function of multimodality reporter strategies will be to provide information about molecular targets in a continuum of research subjects from cells to small animals to human patients.

Targeted imaging of matrix metalloproteinase activity in the evaluation of remodeling tissue-engineered vascular grafts implanted in a growing lamb model

PET and SPECT in epilepsy: A critical review

Molecular imaging techniques apply sophisticated technologies to monitor, directly or indirectly, the spatiotemporal distribution of molecular or cellular processes for biomedical, diagnostic, or therapeutic purposes. For example, Single-Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) imaging, the most representative modalities of molecular imaging, enable earlier and more accurate diagnosis of cancer and cardiovascular diseases. New possibilities for noninvasive molecular imaging in vivo have emerged with advances in bioorthogonal chemistry. For example, tetrazine-related Inverse Electron Demand Diels-Alder (IEDDA) reactions can rapidly generate short-lived radioisotope probes in vivo that provide strong contrast for SPECT and PET. Here, we review pretargeting strategies for molecular imaging and novel radiotracers synthesized via tetrazine bioorthogonal chemistry. We systematically describe advances in direct radiolabeling and pretargeting approaches in SPECT and PET using metal and nonmetal radioisotopes based on tetrazine bioorthogonal reactions, and we discuss prospects for the future of such contrast agents.

ObjectiveDeep learning approaches have attracted attention for improving the scoring accuracy in computed tomography-less single photon emission computed tomography (SPECT). In this study, we proposed a novel deep learning approach referring to positron emission tomography (PET). The aims of this study were to analyze the agreement of representative voxel values and perfusion scores of SPECT-to-PET translation model-generated SPECT (SPECTSPT) against PET in 17 segments according to the American Heart Association (AHA).MethodsThis retrospective study evaluated the patient-to-patient stress, resting SPECT, and PET datasets of 71 patients. The SPECTSPT generation model was trained (stress: 979 image pairs, rest: 987 image pairs) and validated (stress: 421 image pairs, rest: 425 image pairs) using 31 cases of SPECT and PET image pairs using an image-to-image translation network. Forty of 71 cases of left ventricular base-to-apex short-axis images were translated to SPECTSPT in the stress and resting state (stress: 1830 images, rest: 1856 images). Representative voxel values of SPECT and SPECTSPT in the 17 AHA segments against PET were compared. The stress, resting, and difference scores of 40 cases of SPECT and SPECTSPT were also compared in each of the 17 segments.ResultsFor AHA 17-segment-wise analysis, stressed SPECT but not SPECTSPT voxel values showed significant error from PET at basal anterior regions (segments #1, #6), and at mid inferoseptal regions (segments #8, #9, and #10). SPECT, but not SPECTSPT, voxel values at resting state showed significant error at basal anterior regions (segments #1, #2, and #6), and at mid inferior regions (segments #8, #9, and #11). Significant SPECT overscoring was observed against PET in basal-to-apical inferior regions (segments #4, #10, and #15) during stress. No significant overscoring was observed in SPECTSPT at stress, and only moderate over and underscoring in the basal inferior region (segment #4) was found in the resting and difference states.ConclusionsOur PET-supervised deep learning model is a new approach to correct well-known inferior wall attenuation in SPECT myocardial perfusion imaging. As standalone SPECT systems are used worldwide, the SPECTSPT generation model may be applied as a low-cost and practical clinical tool that provides powerful auxiliary information for the diagnosis of myocardial blood flow.

Phase I Study of Noninvasive Imaging of Adenovirus-mediated Gene Expression in the Human Prostate

Noninvasive imaging in the evaluation of a wide variety of cardiovascular diseases has gained an increasing role in the diagnostic strategy in current cardiology practice [1][2][3][4].This holds in particular for patients with myocardial ischaemia due to coronary artery disease (CAD) [5][6][7].Of the present imaging modalities, single-photon emission computed tomography (SPECT), positron emission tomography (PET) and cardiac magnetic resonance (CMR) have attained a major position when it comes to myocardial perfusion imaging [8][9][10][11][12].In the May 2012 issue of the Journal of the American College of Cardiology (JACC), Jaarsma et al. [13] from Maastricht University Medical Center evaluated the diagnostic accuracy of SPECT, PET and CMR for the diagnosis of obstructive CAD.Studies published between 1990 and 2010 identified by PubMed search and citation tracking were examined.A study was included if a perfusion imaging modality was used as a diagnostic test for the detection of obstructive CAD and coronary angiography as the reference standard (50 % diameter luminal stenosis).Out of a total of 3635 studies, 166 articles (including 17,901 patients) met the inclusion criteria: 114 SPECT, 37 CMR, and 15 PET studies.There were insufficient publications on perfusion echocardiography and computed tomography to include these modalities in the study.Patient-based analysis per imaging modality demonstrated pooled sensitivities of 88 % for SPECT, 84 % for PET , and 89 % for CMR; pooled specificities were 61 %, 81 %, and 76 %, respectively.The authors concluded that SPECT, PET, and CMR all yielded high sensitivities, whereas a broad range of specificities were observed.CMR and especially PET showed a significantly higher diagnostic accuracy than SPECT.However, SPECT is more widely available, less expensive, and most extensively validated.In addition, the use of attenuation programs improved the specificity of SPECT.CMR may provide a valid alternative without ionising radiation to the nuclear imaging methods.The authors suggested that referring physicians should consider these findings in the context of local expertise and internal logistics.The authors should be complimented for performing this impressive research.It is the first meta-analysis that has directly compared the three most commonly used techniques for myocardial perfusion imaging, i.e.SPECT, PET, and CMR.The present study emphasises that, from a clinical perspective, each of the studied imaging modalities is in principle suited for detection of abnormalities in myocardial perfusion imaging [14].As always, selective use is mostly dependent on the institutional availability of the imaging device(s), familiarity with the technique, and the individual expert knowledge of the treating physician [15].

The single photon emission computed tomography (SPECT) radiotracer [123I]iomazenil is used to assess benzodiazepine receptor binding parameters. These measurements are relative indices of benzodiazepine receptor concentration (B'max). To evaluate the ability of such indices in accurately accessing the B'max the authors compared them with absolute values of B'max, measured using positron emission tomography (PET). The authors performed SPECT, PET, and magnetic resonance imaging (MRI) studies on a group composed of seven subjects. For SPECT studies, the authors administered a single injection of [123I]iomazenil and estimated the total and specific distribution volumes (DV(T SPECT), DV(S SPECT)) and the binding potential (BP) using unconstrained (BP(SPECT)) and constrained (BP(C SPECT)) compartmental models. For PET studies, the authors used a multiinjection approach with [11C]flumazenil and unlabeled flumazenil to estimate absolute values of receptor concentration, B'max, and some other binding parameters. The authors studied the correlation of different binding parameters with B'max. To study the robustness of the binding parameter measurements at the pixel level, the authors applied a wavelet-based filter to improve signal-to-noise ratio of time-concentration curves, and the calculated kinetic parameters were used to build up parametric images. For PET data, the B'max and the DV(PET) were highly correlated (r = 0.988). This confirms that it is possible to use the DV(PET) to access benzodiazepine receptor density. For SPECT data, the correlation between DV(SPECT) estimated using a two- and three-compartment model was also high (r = 0.999). The DV(T SPECT) and BP(C SPECT) parameters estimated with a constrained three-compartment model or the DV(T''SPECT) parameter estimated with a two-compartment model were also highly correlated to the B'max parameter estimated with PET. Finally, the robustness of the binding parameters allowed the authors to build pixel-by-pixel parametric images using SPECT data.

Molecular imaging, as applied to clinical practice today, is in its early stages. Encouraging advances achieved in clinical positron emission tomography (PET) and small-animal imaging indicate that this technique is evolving into an indispensable diagnostic tool. When employed with complementary morphological imaging procedures, molecular imaging results in substantial diagnostic capability. It will enable the physician to unveil topographic biochemistry in situ and reduce invasive testing. While this is at least in part futuristic, it is clear already today that a comprehensive set of imaging modalities will be required. Imaging modalities most appropriate for molecular imaging are PET, single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), optical imaging, and ultrasound. The foundation for advances in molecular imaging, however, is not primarily imaging hardware development but scientific advancements in molecular biology and progress in probe development. Other factors to consider are postprocessing software and, inevitably, market dynamics. Thus. it implies efficient collaborations across disciplines, agencies, and industries to develop molecular imaging tools for the clinic.

Molecular imaging of breast cancer

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) brain imaging are widely used as diagnostic tools for suspected dementia but no studies have directly compared participant views of the two procedures. We used a range of methods to explore preferences for PET and SPECT. Patients and controls (and accompanying carers) completed questionnaires immediately after undergoing PET and SPECT brain scans. Pulse rate data were collected during each scan. Scan attributes were prioritized using a card sorting exercise; carers and controls additionally answered willingness to pay (WTP) questions. Few differences were found either between the scans or groups of participants, although carers marginally preferred SPECT. Diagnostic accuracy was prioritized over other scan characteristics. Mean heart rate during both scans was lower than baseline heart rate measured at home (p < 0.001). Most participants viewed PET and SPECT scans as roughly equivalent and did not have a preference for either scan. Carer preference for SPECT is likely to reflect their desire to be with the patient (routine practice for SPECT but not for PET), suggesting that they should be able to accompany vulnerable patients throughout imaging procedures wherever possible. Pulse rate data indicated that brain imaging was no more stressful than a home visit (HV) from a researcher. The data do not support the anecdotal view that PET is a more burdensome procedure and the use of PET or SPECT scans in dementia should be based on diagnostic accuracy of the technique.