Accuracy and precision of radioactivity quantification in nuclear medicine images

The ability to reliably quantify activity in nuclear medicine has a number of increasingly important applications. Dosimetry for targeted therapy treatment planning or for approval of new imaging agents requires accurate estimation of the activity in organs, tumors, or voxels at several imaging time points. Another important application is the use of quantitative metrics derived from images, such as the standard uptake value commonly used in positron emission tomography (PET), to diagnose and follow treatment of tumors. These measures require quantification of organ or tumor activities in nuclear medicine images. However, there are a number of physical, patient, and technical factors that limit the quantitative reliability of nuclear medicine images. There have been a large number of improvements in instrumentation, including the development of hybrid single-photon emission computed tomography/computed tomography and PET/computed tomography systems, and reconstruction methods, including the use of statistical iterative reconstruction methods, which have substantially improved the ability to obtain reliable quantitative information from planar, single-photon emission computed tomography, and PET images.     

Prognosis in patients with spontaneous chest pain, a nondiagnostic electrocardiogram, normal cardiac enzymes, and no evidence of severe resting ischemia by quantitative technetium 99m sestamibi tomographic imaging

Background  There are limited data addressing the outcome of patients with normal or near normal myocardial perfusion during chest pain at rest. The purpose of this study was to determine the prognosis of patients with spontaneous chest pain, a normal or nondiagnostic electrocardiogram, no enzymatic evidence of myocardial infarction, and no evidence of severe resting ischemia by quantitative technetium 99m (^99mTc) sestamibi imaging. Methods  In the study, 111 patients who fulfilled the above criteria were injected with ^99mTc sestamibi during resting chest pain and were followed for a median 2.7 years. Of the patients in the study group, 58% had coronary artery disease that was documented by clinical history or coronary angiography. Tomographic ^99mTc perfusion images were interpreted with a quantitative threshold technique initially developed to detect severely hypoperfused myocardium. The images were also interpreted qualitatively to detect patients with milder degrees of hypoperfused myocardium. Results  During follow-up 3 patients had cardiac deaths, 5 had nonfatal myocardial infarctions, and 21 underwent revascularization procedures (13 within 3 months and 8 more than 3 months after the sestamibi study). At 3 years, survival free of cardiac death was 97%, survival free of cardiac death or myocardial infarction was 91%, and survival of cardiac death, myocardial infarction, or late revascularization was 82%. Quantitative analysis of the scans revealed that 100% of patients without fixed defects had 3-year survival free of cardiac death versus 76% of patients who had fixed defects (p<0.001). Mild to moderate resting ischemia by qualitative interpretation of the scans was present in 20% of patients, but this did not predict outcome. Conclusions  Patients with spontaneous chest pain and nonischemic quantitative ^99mTc sestamibi images were at reasonably low risk for hard cardiac events although some patients (18%) required revascularization. Supported in part by the DuPont Merck Pharmaceutical Company, N. Billerica, Mass.     

Interpretation and reporting of myocardial perfusion SPECT: a summary for technologists

Interpretation of cardiac perfusion SPECT images, and the subsequent reporting of results to referring physicians, are sometimes taken to be outside the sphere of the nuclear medicine technologist. However, all personnel involved with nuclear medicine procedures contribute to the timeliness and usefulness of the final report. The goal of this article is to review the principles of scan interpretation and reporting, from the standpoint of what technologists need to understand about these processes. In addition, software tools to aid these processes will be discussed, including quantitative image analysis, telemedicine, computer-aided scan interpretation, databases, computer-aided reporting, and Internet-based reporting. Finally, the accuracy of the scan report will be related to the tasks normally performed by technologists, such as the acquisition and processing of images and the entry, transfer, and networking of data. After reading this article, the reader will be able to describe the principles of scan interpretation and reporting, the software tools for telemedicine and computer-aided interpretation, and the role of the technologist in this process.     

Is metal artefact reduction mandatory in cardiac PET/CT imaging in the presence of pacemaker and implantable cardioverter defibrillator leads?

Purpose  

Cardiac PET/CT imaging is often performed in patients with pacemakers and implantable cardioverter defibrillator (ICD) leads. However, metallic implants usually produce artefacts on CT images which might propagate to CT-based attenuation-corrected (CTAC) PET images. The impact of metal artefact reduction (MAR) for CTAC of cardiac PET/CT images in the presence of pacemaker, ICD and ECG leads was investigated using both qualitative and quantitative analysis in phantom and clinical studies.     

Challenges for measurement of myocardial perfusion and perfusion reserve by SPECT imaging

Conclusions  The present study by Storto et al¹ provides additional evidence that quantitative estimates of myocardial perfusion and perfusion reserve can be derived from SPECT myocardial perfusion images by use of equipment, tracers, and techniques that are available in most nuclear cardiology laboratories. Additional clinical studies are needed to optimize the methods used to derive the quantitative estimates of perfusion and perfusion reserve from the SPECT imaging studies and, ultimately, to determine the applicability of these measurements to the daily practice of nuclear cardiology.     

Corridor4DM: The Michigan method for quantitative nuclear cardiology

Quantitative software for the analysis and review of myocardial perfusion emission computed tomography images is an indispensable tool in the nuclear physician’s evaluation of patients with known or suspected heart disease. The Corridor4DM (4DM) application (formerly known as 4DM-SPECT), developed at the University of Michigan Medical Center, is a quantitative software application providing automated processing, analysis, and reporting of myocardial perfusion and function from cardiac emission computed tomography studies in a tightly integrated, user-centered environment. With health care placing increased emphasis on higher quality and efficiency in diagnostic imaging, quantitative analysis and review software applications need to provide a comprehensive environment supporting correlative review of multimodality images, integrated report generation, and remote review capabilities. The current and future design capabilities of the 4DM software application are discussed with respect to the changing landscape of imaging, where cardiac computed tomography, positron emission tomography, structured reporting, and remote review are expanding the base requirement specifications for quantitative software.     

Parametric images via dynamic <Superscript>18</Superscript>F-fluorodeoxyglucose positron emission tomographic data acquisition in predicting midterm outcome of liver metastases secondary to gastrointestinal stromal tumours

Purpose  

¹⁸F-Fluorodeoxyglucose positron emission tomography (FDG PET) may underestimate viable tumour tissue in patients with gastrointestinal stromal tumours (GIST) treated with molecular targeted agents. The aim of the present study was to investigate the value of parametric images generated after dynamic data acquisition for the detection of active liver metastases.     

Cardiovascular molecular imaging

The recent introduction of novel gene therapies for treatment of cardiac and noncardiac diseases has caused a remarkable need for noninvasive imaging approaches to evaluate and track the progress of these therapies. In the past we have relied on the evaluation of the physiological consequences of therapeutic interventions. With advances in targeted molecular imaging we now have the ability to evaluate early molecular effects of these therapies. The development of dedicated high resolution small animal imaging systems and the establishment of transgenic animal models has enhanced our understanding of cardiovascular disease and has expedited the development of new gene therapies. Noninvasive targeted molecular imaging will allow us to directly track biochemical processes and signaling events that precede the pathophysiological changes. The examples of targeted molecular imaging outlined in this seminar provide some insight into the bright and growing future of cardiovascular molecular imaging. The success of this new field rests on the development of targeted biological markers of molecular and physiological processes, development of new instruments with improved sensitivity and resolution, and the establishment of multidisciplinary teams of experimental and clinical investigators with a wide range of expertise. Molecular imaging already plays a critical role in the experimental laboratory. We expect that, in the near future, targeted molecular imaging will be routinely used in clinical cardiovascular nuclear medicine laboratories in conjunction with existing imaging modalities for both diagnostic and prognostic purposes, as well as for evaluation of new genetic based therapeutic strategies.     

Acute myocardial perfusion imaging for the technologist

Conclusion  Acute myocardial perfusion imaging involves careful planning from the nuclear medicine or nuclear cardiology laboratory to ensure optimal results are achieved. The role of the technologist is to ensure a high-quality study is performed on every patient who is referred to the laboratory. This is one of the most important roles because the decision for further evaluation can be based on the interpretation of the acute images. When acute myocardial perfusion imaging is used appropriately, in conjunction with standard methods of evaluation for patients presenting to the emergency department with chest pain syndromes perceived to be cardiac in origin, it can be of great benefit. It offers a more definitive diagnosis of chest pain syndromes and can be used to reduce the expense of otherwise costly hospital stays, even in patients with moderate risk of ischemic heart disease.     

Automated three-dimensional quantification of myocardial perfusion and brain SPECT.

To allow automated and objective reading of nuclear medicine tomography, we have developed a set of tools for clinical analysis of myocardial perfusion tomography (PERFIT) and Brain SPECT/PET (BRASS). We exploit algorithms for image registration and use three-dimensional (3D) "normal models" for individual patient comparisons to composite datasets on a "voxel-by-voxel basis" in order to automatically determine the statistically significant abnormalities. A multistage, 3D iterative inter-subject registration of patient images to normal templates is applied, including automated masking of the external activity before final fit. In separate projects, the software has been applied to the analysis of myocardial perfusion SPECT, as well as brain SPECT and PET data. Automatic reading was consistent with visual analysis; it can be applied to the whole spectrum of clinical images, and aid physicians in the daily interpretation of tomographic nuclear medicine images.     

Temporally targeted imaging method applied to ECG-gated computed tomography: preliminary phantom and in vivo experience

RATIONALE AND OBJECTIVES: Existing cardiac imaging methods do not allow for improved temporal resolution when considering a targeted region of interest (ROI). The imaging method presented here enables improved temporal resolution for ROI imaging (namely, a reconstruction volume smaller than the complete field of view). Clinically, temporally targeted reconstruction would not change the primary means of reconstructing and evaluating images, but rather would enable the adjunct technique of ROI imaging, with improved temporal resolution compared with standard reconstruction ( approximately 20% smaller temporal scan window). In gated cardiac computed tomography (CT) scans improved temporal resolution directly translates into a reduction in motion artifacts for rapidly moving objects such as the coronary arteries. MATERIALS AND METHODS: Retrospectively electrocardiogram gated coronary angiography data from a 64-slice CT system were used. A motion phantom simulating the motion profile of a coronary artery was constructed and scanned. Additionally, an in vivo study was performed using a porcine model. Comparisons between the new reconstruction technique and the standard reconstruction are given for an ROI centered on the right coronary artery, and a pulmonary ROI. RESULTS: In both a well-controlled motion model and a porcine model results show a decrease in motion induced artifacts including motion blur and streak artifacts from contrast enhanced vessels within the targeted ROIs, as assessed through both qualitative and quantitative observations. CONCLUSION: Temporally targeted reconstruction techniques demonstrate the potential to reduce motion artifacts in coronary CT. Further study is warranted to demonstrate the conditions under which this technique will offer direct clinical utility. Improvement in temporal resolution for gated cardiac scans has implications for improving: contrast enhanced CT angiography, calcium scoring, and assessment of the pulmonary anatomy.     

Dual “motion-frozen heart” combining respiration and contraction compensation in clinical myocardial perfusion SPECT imaging

Objectives  This article assesses the effect of a new correction technique (“motion-frozen heart”) which compensates for the previously described nonuniform blurring of myocardial perfusion imaging (MPI) due to respiration motion or cardiac contraction. Methods  Respiratory and ECG-gated one-day ^99mTc-MIBI MPI studies performed in 48 patients were evaluated. MPI scans were acquired on a gamma camera supporting list-mode functionality synchronized with an external respiratory strap and an ECG device. Respiratory and cardiac-gated bins were generated using the acquired list file. Respiratory-gated bins were corrected for respiratory motion, followed by correction for cardiac contraction motion. In addition, cardiac contraction correction was applied to cardiac-gated bins uncorrected for respiratory motion. Bullseye maps were generated for uncorrected MPI studies, as well as following correction for respiratory motion, cardiac contraction, and both. The mean difference between each of the correction vs the uncorrected bullseye was calculated. Visual assessment of image quality, severity, and extent of the uncorrected perfusion images and following each of the corrections was performed. Results  Average motion due respiration was 7.0 ± 2.6 mm in the axial plane. The maximal score difference in segmental uptake greater than 10% was found in 2%, 15%, and 25% following respiratory correction, contraction correction, and dual corrections, respectively. Percent of scans classified with an excellent image quality was 13%, 21%, 42%, and 52% for the uncorrected images and following respiratory correction, contraction correction, and dual corrections, respectively. Conclusions  A technique that compensates for motion of the heart due to respiration and cardiac contraction in MPI-SPECT was evaluated. Compensating for both respiration and cardiac contraction had the greatest effect on perfusion images resulting in significantly improved image quality.     

Redesigning the nuclear medicine reading room

The process of image review and interpretation has become increasingly complex and challenging for today's nuclear medicine physician from many perspectives, especially with regard to workstation integration and reading room ergonomics. With the recent proliferation of hybrid imaging systems, this complexity has increased rapidly, along with the number of studies performed. At the same time, clinicians throughout the health care enterprise are expecting remote access to nuclear medicine images whereas nuclear medicine physicians require reliable access at the point of care to the electronic medical record and to medical images from radiology and cardiology. The authors discuss the background and challenges related to integration of nuclear medicine into the health care enterprise and provide a series of recommendations for advancing successful integration efforts. Also addressed are unique characteristics of the nuclear medicine environment as well as ergonomic, lighting, and environmental considerations in the design and redesign of the modern reading room.     

Spect attenuation correction: an essential tool to realize nuclear cardiology’s manifest destiny

Single photon emission computed tomography (SPECT) myocardial perfusion imaging has attained widespread clinical acceptance as a standard of care for cardiac patients. Yet, physical phenomena degrade the accuracy of how our cardiac images are visually interpreted or quantitatively analyzed. This degradation results in cardiac images in which brightness or counts are not necessarily linear with tracer uptake or myocardial perfusion. Attenuation correction (AC) is a methodology that has evolved over the last 30 years to compensate for this degradation. Numerous AC clinical trials over the last 10 years have shown increased diagnostic accuracy over non-AC SPECT for detecting and localizing coronary artery disease, particularly for significantly increasing specificity and normalcy rate. This overwhelming evidence has prompted our professional societies to issue a joint position statement in 2004 recommending the use of AC to maximize SPECT diagnostic accuracy and clinical usefulness. Phantom and animal studies have convincingly shown how SPECT AC recovers the true regional myocardial activity concentration, while non-AC SPECT does not. Thus, AC is also an essential tool for extracting quantitative parameters from all types of cardiac radionuclide distributions, and plays an important role in establishing cardiac SPECT for flow, metabolic, innervation, and molecular imaging, our manifest destiny. (J Nucl Cardiol 2007;14:16–24.)     

Whole heart magnetization‐prepared steady‐state free precession coronary vein MRI

Purpose

To compare two coronary vein imaging techniques using whole‐heart balanced steady‐state free precession (SSFP) and a targeted double‐oblique spoiled gradient‐echo (GRE) sequences in combination with magnetization transfer (MT) preparation sequence for tissue contrast improvement.

Materials and Methods

Nine healthy subjects were imaged with the proposed technique. The results are compared with optimized targeted MT prepared GRE acquisitions. Both quantitative and qualitative analyses were performed to evaluate each imaging method.

Results

Whole‐heart images were successfully acquired with no visible image artifact in the vicinity of the coronary veins. The anatomical features and visual grading of both techniques were comparable. However, the targeted small slab acquisition of the left ventricular lateral wall was superior to whole‐heart acquisition for visualization of relevant information for cardiac resynchronization therapy (CRT) lead implantation.

Conclusion

We demonstrated the feasibility of whole‐heart coronary vein MRI using a 3D MT‐SSFP imaging sequence. A targeted acquisition along the lateral left ventricular wall is preferred for visualization of branches commonly used in CRT lead implantation. J. Magn. Reson. Imaging 2009;29:1293–1299. © 2009 Wiley‐Liss, Inc.     

Diagnostic accuracy and agreement between whole-body diffusion MRI and bone scintigraphy in detecting bone metastases

Purpose

This study was done to determine the diagnostic value of whole-body magnetic resonance using diffusion-weighted imaging with background suppression (WB-DWIBS) for detecting bone metastases compared with whole-body bone scintigraphy (WB-BS).

Materials and methods

Twenty-three patients with solid tumours underwent both WB-DWIBS imaging and WBBS. A nuclear medicine specialist interpreted WB-BS images and two blinded radiologists, first independently and then jointly, interpreted the WB-DWIBS images by completing a reading grid categorising the skeletal segments. Cohen’s k statistic was used to determine interobserver agreement in reading the WB-DWIBS images and the agreement between WB-BS and WB-DWIBS. Sensitivity and specificity were calculated per patient and per lesion.

Results

Interobserver agreement in reading the WBDWIBS images was substantial or good, with κ=0.68. Analysis of agreement between the nuclear physician’s and the radiologists’ readings provided κ=0.87 [95% confidence interval (CI)=0.76–0.98)] Per-lesion analysis gave a sensitivity of 80% (95% CI=75–85) and a specificity of 98.2% (95% CI=96.5–99.8).

Conclusions

We found a good level of interobserver agreement for the WB-DWIBS images and an excellent level of agreement in the subjective judgement of presence or absence of disease between WB-BS and WB-DWIBS after consensual double reading. WB-DWIBS has the same specificity as WB-BS in detecting bone metastases. The anatomical sites exhibiting the highest level of disagreement between WB-DWIBS and WB-BS are the pelvis, the coccyx, and the sternum, all sites at which detection with WB-BS has the greatest limitations.     

Analysis of myocardial perfusion from vasodilator stress computed tomography: Does improvement in image quality by iterative reconstruction lead to improved diagnostic accuracy?

BackgroundIterative reconstruction (IR) in cardiac CT has been shown to improve confidence of interpretation of noninvasive coronary CT angiography (CTA).ObjectiveWe hypothesized that IR would also improve the quality of vasodilator stress coronary CT images acquired with low tube voltage to assess myocardial perfusion and the accuracy of the detection of perfusion abnormalities by using quantitative 3-dimensional (3D) analysis.MethodsWe studied 39 consecutive patients referred for coronary CTA (256-slice scanner; Philips), who underwent additional imaging (100 kV, prospective gating) with regadenoson (0.4 mg; Astellas). Stress images were reconstructed with different algorithms: filtered back projection (FBP) and IR (iDose; Philips). Image quality was quantified by signal-to-noise and contrast-to-noise ratios in the blood pool and the myocardium. Then, FBP and separately IR images were analyzed with custom 3D analysis software to quantitatively detect perfusion defects. Accuracy of detection was compared with perfusion abnormalities predicted by coronary stenosis >50% on coronary CTA.ResultsFive patients with image artifacts were excluded. In the remaining 34 patients, both signal-to-noise and contrast-to-noise ratios increased with IR, indicating improvement in image quality compared with FBP. For 3D perfusion analysis, 10 patients with normal coronary arteries were used as a reference to correct for x-ray attenuation variations in normal myocardium. In the remaining 24 patients, reduced noise levels in the IR images compared with FBP resulted in tighter attenuation distribution and improved detection of perfusion abnormalities.ConclusionIR significantly improves image quality on regadenoson stress CT images acquired with low tube voltage, leading to improved 3D quantitative evaluation of myocardial perfusion.     

The additive prognostic value of perfusion and functional data assessed by quantitative gated SPECT in women

Background  The aim of this study was to assess the prognostic value of technetium-99m tetrofosmin gated SPECT imaging in women using quantitative gated single photon emission computed tomography (SPECT) imaging. Methods  We followed 453 consecutive female patients. Average follow-up was 1.33 years (max. 2.55). Hard endpoints were cardiac death, acute myocardial infarction, or documented ventricular fibrillation. Event-free survival curves were obtained. Optimal cutoff values for left ventricular (LV) volumes, LV ejection fraction (LVEF), and perfusion data to predict outcome were determined by ROC curve analysis. Results  A total of 236 patients had an abnormal study, of whom 27 patients experienced hard events (16 deaths) and 47 patients soft events. For hard events summed stress score (SSS) and LVEF, and for any cardiac event SSS showed independent incremental prognostic value. The survival curves were maximally separated when using cutoff values for SSS of ≥22 and LVEF < 52% (P < 0.001, HR 4.61 and P < 0.001 HR 5.24 for SSS and LVEF resp.), and SSS ≥ 14 (P < 0.001 HR 3.76) for any cardiac event. Conclusion  In women, perfusion and functional parameters derived from quantitative gated technetium-99m tetrofosmin SPECT imaging can adequately be used for cardiac risk assessment. Using quantitative gated SPECT, female patients with an LVEF < 52% or an SSS ≥ 22 are at increased risk for subsequent hard events. Furthermore, patients with an SSS ≥ 14 are at increased risk for any cardiac events.     

Nanoparticle pharmacokinetic profiling in vivo using magnetic resonance imaging

Contrast agents targeted to molecular markers of disease are currently being developed with the goal of identifying disease early and evaluating treatment effectiveness using noninvasive imaging modalities such as MRI. Pharmacokinetic profiling of the binding of targeted contrast agents, while theoretically possible with MRI, has thus far only been demonstrated with more sensitive imaging techniques. Paramagnetic liquid perfluorocarbon nanoparticles were formulated to target α_vβ₃‐integrins associated with early atherosclerosis in cholesterol‐fed rabbits to produce a measurable signal increase on magnetic resonance images after binding. In this work, we combine quantitative information of the in vivo binding of this agent over time obtained by means of MRI with blood sampling to derive pharmacokinetic parameters using simultaneous and individual fitting of the data to a three compartment model. A doubling of tissue exposure (or area under the curve) is obtained with targeted as compared to control nanoparticles, and key parameter differences are discovered that may aid in development of models for targeted drug delivery. Magn Reson Med 60:1353–1361, 2008. © 2008 Wiley‐Liss, Inc.     

123I-mIBG Scintigraphy to predict risk for adverse cardiac outcomes in heart failure patients: Design of two prospective multicenter international trials

Background  ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) consists of two identical prospective open-label, multicenter, phase 3 studies (MBG311 and MBG312) evaluating the prognostic usefulness of ¹²³I-mIBG scintigraphy for identifying subjects with heart failure who will experience a major adverse cardiac event. Methods  Subjects with NYHA class II and III heart failure and left ventricular ejection fraction ≤35% were eligible for the trials. Subjects underwent planar and SPECT ¹²³I-mIBG myocardial imaging, as well as echocardiography and gated SPECT ^99mTc-tetrofosmin myocardial perfusion imaging. Subjects are then monitored on a regular basis for 2 years. Time to first occurrence of one of the following—NYHA class progression; potentially life-threatening arrhythmic event (including ICD discharge); or cardiac death, as verified by an independent adjudication panel—will be analyzed in comparison to quantitative parameters derived from ¹²³I-mIBG imaging. The primary efficacy analysis will employ the heart/mediastinum ratio on 4-hour delayed planar imaging, while secondary efficacy analyses will examine quantitative results from both planar and SPECT ¹²³I-mIBG images, as well as from ^99mTc-tetrofosmin SPECT and echocardiography. Conclusion  The results of the ADMIRE-HF trials will provide prospective validation of the potential role of ¹²³I-mIBG scintigraphy in assessing prognosis and developing management strategies for patients with heart failure. Funding Source: GE Healthcare.