Nuclear Medicine Imaging Tools in Fever of Unknown Origin: Time for a Revisit and Appropriate Use Criteria.

Fever of unknown origin (FUO) is a clinical conundrum for patients and clinicians alike, and imaging studies are often performed as part of the diagnostic workup of these patients. Recently, the Society of Nuclear Medicine and Molecular Imaging convened and approved a guideline on the use of nuclear medicine tools for FUO. The guidelines support the use of 2-18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in adults and children with FUO. 18F-FDG PET/CT allows detection and localization of foci of hypermetabolic lesions with high sensitivity because of the 18F-FDG uptake in glycolytically active cells that may represent inflammation, infection, or neoplasia. Clinicians should consider and insurers should cover 18F-FDG PET/CT when evaluating patients with FUO, particularly when other clinical clues and preliminary studies are unrevealing.

Musculoskeletal Infection: Role of Molecular Imaging in Diagnosis and Monitoring Treatment Response.

Molecular imaging tests frequently are performed as part of the diagnostic workup of musculoskeletal infection. Three-phase bone scintigraphy reliably diagnoses osteomyelitis in bones not affected by underlying conditions. The test is less useful, because of decreased specificity, in patients with underlying bony abnormalities or alterations such as fractures, orthopaedic hardware, arthritic changes, and tumors. At one time gallium-67 scintigraphy was used as a complement to bone scintigraphy to improve the specificity of diagnosis. With the introduction of labeled leukocytes and, more recently, fluorine-18 fluorodeoxyglucose, gallium-67 is reserved primarily for spinal infections when fluorine-18 fluorodeoxyglucose is not available. Except for the spine, in vitro labeled leukocyte imaging is valuable for diagnosing osteomyelitis in the setting of underlying osseous abnormalities. Leukocytes accumulate in bone marrow as well as in the presence of infection. Performing complementary bone marrow imaging with technetium-99m sulfur colloid facilitates the differentiation between the two and improves test accuracy. Fluorine-18 fluorodeoxyglucose accurately diagnoses spondylodiskitis and diabetic foot osteomyelitis, but its value in periprosthetic joint infection has yet to be determined.

A Brief History of Nuclear Medicine Imaging of Infection.

For nearly 50 years, nuclear medicine has played an important role in the diagnosis of infection. Gallium citrate Ga 67 was one of the first, if not the first, radionuclide used for this purpose. Unfavorable imaging characteristics, a lack of specificity, and the long interval (2-3 days) between administration and imaging spurred the search for alternatives. At the present time, gallium 67 citrate is used primarily for differentiating acute tubular necrosis from interstitial nephritis and as an alternative for indications including sarcoid, spondylodiscitis, and fever of unknown origin, when 18F-fluorodeoxyglucose (18F-FDG) is not available. The approval, in the mid-1980s, of techniques for in vitro labeling of leukocytes with indium-111 and technetium-99m that subsequently migrate to foci of infection was a significant advance in nuclear medicine imaging of infection and labeled leukocyte imaging still plays an important role in imaging of infection. There are significant disadvantages to in vitro labeled leukocyte imaging. Unfortunately, efforts devoted to developing in vivo leukocyte labeling methods have met with only limited success. Over the past 20 years 18F-FDG has established itself as a valuable imaging agent for musculoskeletal and cardiovascular infections, as well as sarcoidosis and fever of unknown origin. As useful as these agents are, their uptake is based on the host response to infection, not infection itself. Previous attempts at developing infection-specific agents, including radiolabeled antibiotics and vitamins, were limited by poor results and/or lack of availability, so investigators continue to focus on developing infection-specific nuclear medicine imaging agents.

99mTc-PYP SPECT and SPECT/CT quantitation for diagnosing cardiac transthyretin amyloidosis.

BACKGROUND: We investigated quantitative 99mTc-pyrophosphate (PYP) SPECT/CT reproducibility and accuracy for diagnosing cardiac transthyretin amyloidosis (ATTR), and whether SPECT/CT improved visual and quantitative results compared to SPECT-only. METHODS: Data were reviewed for 318 patients with suspected ATTR who underwent PYP SPECT/CT. Myocardial-to-blood pool count (MBP) ratios were computed and repeated independently > 1 month later. A physician independently scored LV myocardial-to-rib uptake on SPECT/CT as: 0 (negative), 1 < rib (equivocal), 2 = rib (positive) or 3 > rib (positive), and the image quality as: 1 (poor), 2 (adequate), and 3 (good). SPECT-only MBP ratios and visual scores were assessed separately for a subgroup of the first sequential 191 patients. RESULTS: 25% of patients had positive myocardial uptake (myocardial-to-rib uptake score of ≥ 2). SPECT/CT MBP ratios were reproducible (1.35 ± .68 vs 1.33 ± .74, p = .09) and corresponded with visual scores ≥ 2 (ROC AUC = 99 ± 1%) more accurately than SPECT-only MBPs (93 ± 3%, p = .02). SPECT/CT image quality was better than that of SPECT-only (2.7 ± .5 vs 2.1 ± .5, p < .0001) with fewer equivocal results (2.6% vs 22.5%, p < .0001). CONCLUSION: SPECT/CT produces MBP ratios that are reproducible and accurately identify a positive scan, with better image quality and fewer equivocal cases than SPECT-only.

FDG PET in Evaluation of Patients With Fever of Unknown Origin: AJR Expert Panel Narrative Review.

Fever of unknown origin (FUO) is a diagnostic challenge, with its cause remaining undiagnosed in approximately half of patients. Nuclear medicine tests typically are performed after a negative or inconclusive initial workup. Gallium-67 citrate and labeled leukocytes were previous mainstays of radionuclide imaging for FUO, although they had limited diagnostic performance. FDG PET/CT has subsequently emerged as the nuclear medicine imaging test of choice, supported by a growing volume of evidence. A positive FDG PET/CT result contributes useful information by identifying potential causes of fever, localizing sites for further evaluation, and guiding further management; a negative result contributes useful information by excluding focal disease as the cause of fever and predicts a favorable prognosis. In 2021, CMS rescinded a prior national noncoverage determination for FDG PET for infection and inflammation, leading to increasing national utilization of FDG PET/CT for FUO workup. This article reviews the current status of the role of FDG PET/CT in the evaluation of patients with FUO. The literature reporting the diagnostic performance and yield of FDG PET/CT in FUO workup is summarized, with comparison with historically used nuclear medicine tests included. Attention is also given to the test's clinical impact; protocol, cost, and radiation considerations; and application in children.

Clinical implications of compromised 82Rb PET data acquisition.

BACKGROUND: We wished to document the prevalence and quantitative effects of compromised 82Rb PET data acquisitions on myocardial flow reserve (MFR). METHODS AND RESULTS: Data were analyzed retrospectively for 246 rest and regadenoson-stress studies of 123 patients evaluated for known or suspected CAD. An automated injector delivered pre-determined activities of 82Rb. Automated quality assurance algorithms identified technical problems for 7% (9/123) of patients. Stress data exhibited 2 instances of scanner saturation, 1 blood peak detection, 1 blood peak width, 1 gradual patient motion, and 2 abrupt patient motion problems. Rest data showed 1 instance of blood peak width and 2 abrupt patient motion problems. MFR was lower for patients with technical problems flagged by the quality assurance algorithms than those without technical problems (1.5 ± 0.5 versus 2.1 ± 0.7, P = 0.01), even though rest and stress ejection fraction, asynchrony and relative myocardial perfusion measures were similar for these two groups (P > 0.05), suggesting that MFR accuracy was adversely affected by technical errors. CONCLUSION: It is important to verify integrity of 82Rb data to ensure MFR computation quality.

Early onset of left ventricular regional asynchrony in arteries with sub-clinical stenosis.

BACKGROUND: Asynchrony has been reported to be a marker of ischemic-induced left ventricular dysfunction, the magnitude of which correlates with extent of epicardial coronary disease. We wished to determine whether normal-appearing arterial territories with mild degrees of asynchrony have lower 82Rb PET absolute myocardial blood flow (MBF) and/or lower myocardial flow reserve (MFR). METHODS AND RESULTS: Data were examined retrospectively for 105 patients evaluated for known/suspected CAD who underwent rest/regadenoson-stress 82Rb PET/CT and quantitative coronary angiography. Rest and stress absolute MBF and MFR were quantified from first-pass 82Rb PET curves. Regional relative myocardial perfusion summed stress score (SSS), summed rest score (SRS), regional phase bandwidth (BW), and regional semi-quantitative asynchrony visual scores of (Asynch) were assessed. We found that in apparently normal arteries (SSS < 4, SRS < 4 and stenosis < 70%), those with abnormally low MFR < 2.0 compared to those with MFR ≥ 2.0 had larger phase BW (186 ± 79° vs 158 ± 67°, P = .02), and more visually apparent Asynch (5.7 ± 4.2 vs 3.9 ± 3.6, P = .02), which was associated with increasing stenosis values (ρ = 0.44, P < .0001). CONCLUSION: A subgroup of coronary territories with normal relative perfusion and normal or non-obstructive coronary disease may have reduced MFR, which is signaled physiologically by a mild degree of left ventricular asynchrony.

Computational approaches to detect small lesions in 18 F-FDG PET/CT scans.

PURPOSE: When physicians interpret 18 F-FDG PET/CT scans, they rely on their subjective visual impression of the presence of small lesions, the criteria for which may vary among readers. Our investigation used physical phantom scans to evaluate whether image texture analysis metrics reliably correspond to visual criteria used to identify lesions and accurately differentiate background regions from sub-centimeter simulated lesions. METHODS: Routinely collected quality assurance test data were processed retrospectively for 65 different 18 F-FDG PET scans performed of standardized phantoms on eight different PET/CT systems. Phantoms included 8-, 12-, 16-, and 25-mm diameter cylinders embedded in a cylindrical water bath, prepared with 2.5:1 activity-to-background ratio emulating typical whole-body PET protocols. Voxel values in cylinder regions and background regions were sampled to compute several classes of image metrics. Two experienced physicists, blinded to quantified image metrics and to each other's readings, independently graded cylinder visibility on a 5-level scale (0 = definitely not visible to 4 = definitely visible). RESULTS: The three largest cylinders were visible in 100% of cases with a mean visibility score of 3.3 ± 1.2, while the smallest 8-mm cylinder was visible in 58% of cases with a significantly lower mean visibility score of 1.5±1.1 (P < 0.0001). By ROC analysis, the polynomial-fit signal-to-noise ratio was the most accurate at discriminating 8-mm cylinders from the background, with accuracy greater than visual detection (93% ± 2% versus 76% ± 4%, P = 0.0001), and better sensitivity (94% versus 58%, P < 0.0001). CONCLUSION: Image texture analysis metrics are more sensitive than visual impressions for detecting sub-centimeter simulated lesions. Therefore, image texture analysis metrics are potentially clinically useful for 18 F-FDG PET/CT studies.

Relationship of 82Rb PET territorial myocardial asynchrony to arterial stenosis.

OBJECTIVE: 82Rb PET/CT rest/regadenoson-stress data enable quantification of left ventricular rest and stress function, perfusion, and asynchrony. Our study was conducted to determine which parameters best identify patients with multi-vessel disease (MVD) and individual stenosed arteries. METHODS: PET/CT data were reviewed retrospectively for 105 patients referred for evaluation of CAD, who also underwent angiography. % arterial stenosis was determined quantitatively at a core laboratory. Severe stenosis was defined as ≥ 70%, and MVD as 2 or more stenosed arteries. Segmental MBF was calculated from first-pass data for arterial territories. Regional rest and stress systolic and diastolic asynchrony (Asynch) scores were determined from visual examination of phase polar maps. RESULTS: 65 vessels had stenoses ≥ 70%. 15 patients had MVD. ROC area under curve (ROC AUC) for identifying patients with MVD was 83% for Asynch and 73% for MFR. ROC AUC for identifying individual arterial territories with stenoses ≥ 70% was 81% and 72% for Asynch and MFR. CONCLUSION: 82Rb PET/CT accurately identified patients with MVD and individual stenosed territories, with regional asynchrony measurements contributing significantly to identify patients with CAD.

A humanized mouse model of liver fibrosis following expansion of transplanted hepatic stellate cells.

Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as hepatic injuries may cause their transdifferentiation into myofibroblast-like cells capable of producing excessive extracellular matrix proteins. Also, HSCs can modulate engraftment of transplanted hepatocytes and contribute to liver regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is important, but effective methods have not been available to address their fate in vivo. To investigate whether HSCs could engraft and repopulate the liver, we transplanted GFP-transduced immortalized hHSCs into immunodeficient NOD/SCID mice. Biodistribution analysis with radiolabeled hHSCs showed that after intrasplenic injection, the majority of transplanted cells rapidly translocated to the liver. GFP-immunohistochemistry demonstrated that transplanted hHSCs engrafted alongside hepatic sinusoids. Prior permeabilization of the sinusoidal endothelial layer with monocrotaline enhanced engraftment of hHSCs. Transplanted hHSCs remained engrafted without relevant proliferation in the healthy liver. However, after CCl4 or bile duct ligation-induced liver damage, transplanted hHSCs expanded and contributed to extracellular matrix production, formation of bridging cell-septae and cirrhosis-like hepatic pseudolobules. CCl4-induced injury recruited hHSCs mainly to zone 3, whereas after bile duct ligation, hHSCs were mainly in zone 1 of the liver lobule. Transplanted hHSCs neither transdifferentiated into other cell types nor formed tumors in these settings. In conclusion, a humanized mouse model was generated by transplanting hHSCs, which proliferated during hepatic injury and inflammation, and contributed to liver fibrosis. The ability to repopulate the liver with transplanted hHSCs will be particularly significant for mechanistic studies of cell-cell interactions and fibrogenesis within the liver.

Kupffer Cell Transplantation in Mice for Elucidating Monocyte/Macrophage Biology and for Potential in Cell or Gene Therapy.

Kupffer cells (KC) play major roles in immunity and tissue injury or repair. Because recapitulation of KC biology and function within liver will allow superior insights into their functional repertoire, we studied the efficacy of the cell transplantation approach for this purpose. Mouse KC were isolated from donor livers, characterized, and transplanted into syngeneic recipients. To promote cell engraftment through impairments in native KC, recipients were preconditioned with gadolinium chloride. The targeting, fate, and functionality of transplanted cells were evaluated. The findings indicated that transplanted KC engrafted and survived in recipient livers throughout the study period of 3 months. Transplanted KC expressed macrophage functions, including phagocytosis and cytokine expression, with or without genetic modifications using lentiviral vectors. This permitted studies of whether transplanted KC could affect outcomes in the context of acetaminophen hepatotoxicity or hepatic ischemia-reperfusion injury. Transplanted KC exerted beneficial effects in these injury settings. The benefits resulted from cytoprotective factors including vascular endothelial growth factor. In conclusion, transplanted adult KC were successfully targeted and engrafted in the liver with retention of innate immune and tissue repair functions over the long term. This will provide excellent opportunities to address critical aspects in the biogenesis, fate, and function of KC within their native liver microenvironment and to develop the cell and gene therapy potential of KC transplantation.

Relationships between left ventricular asynchrony and myocardial blood flow.

OBJECTIVE: 82Rb PET protocols enable determination of left ventricular asynchrony (LVAS) at rest and stress, along with myocardial blood flow (MBF). We hypothesized that in patients with resting LVAS, MBF differs between those with stress-induced LVAS improvement and those with stress-induced LVAS deterioration. METHODS: We retrospectively analyzed 82Rb rest/regadenoson stress PET studies of 195 patients evaluated for known or suspected coronary artery disease. MBF was computed from first-pass data; function and relative perfusion were computed from myocardial equilibrium data. LVAS was defined as phase contraction bandwidth (BW) above 82Rb gender-specific normal limits, with changes defined as BW moving into or out of normal ranges. RESULTS: Among the 195 patients, 64 had LVAS at rest, of whom 13 reverted to normal and 51 continued to have LVAS with stress. Patients who did not improve had lower stress MBF (1.04 ± 0.69 vs 1.58 ± 0.67, p = .02) and coronary flow reserve (1.94 ± 1.16 vs 3.04 ± 1.22, p = .01) than those who did improve. ROC analysis indicated that the parameter most strongly associated with improvement in asynchrony for patients with resting LVAS was reduction in MBF heterogeneity (ROC area (accuracy) = 84%, sensitivity = 92%, and specificity = 67%). CONCLUSION: LVAS is highly correlated with MBF and CVR, with stress-induced improvement in synchronicity most strongly associated with improved MBF homogeneity.

Directly acting drugs prostacyclin or nitroglycerine and endothelin receptor blocker bosentan improve cell engraftment in rodent liver.

UNLABELLED: To optimize strategies for liver-directed cell therapy, prevention of initial transplanted cell losses is particularly important for subsequent liver repopulation. After cell transplantation in hepatic sinusoids, perturbations in hepatic microcirculation along with changes in various liver cell types are among the earliest changes. Therefore, for advancing further concepts in cell engraftment we studied vascular and related events in the liver after transplanting syngeneic hepatocytes into dipeptidyl peptidase IV-deficient rats. We treated rats with vascular drugs to define whether deleterious cell transplantation-induced events could be controlled followed by improvements in transplanted cell engraftment and proliferation. We found cell transplantation altered liver gene expression related to vessel tone, inflammation, cell adhesion, thrombosis, or tissue damage/remodeling. This was due to hepatic ischemia, endothelial injury, and activation of neutrophils, Kupffer cells, and hepatic stellate cells. Treatment of rats before cell transplantation with the angiotensin converting enzyme blocker, lisinopril, or angiotensin II receptor blocker, losartan, did not improve cell engraftment. By contrast, direct-acting nitroglycerine or prostacyclin improved cell engraftment and also kinetics of liver repopulation. These drugs lowered hepatic ischemia and inflammation, whereas pretreatment of rats with the dual endothelin-1 receptor blocker, bosentan, improved cell engraftment independently of hepatic ischemia or inflammation, without improving liver repopulation. However, incubation of hepatocytes with bosentan protected cells from cytokine toxicity in vitro and produced superior cell engraftment and proliferation in vivo. CONCLUSION: Cell transplantation-induced changes in hepatic microcirculation contributed to transplanted cell clearances from liver. Vascular drugs, such as nitroglycerine, prostacyclin, and bosentan, offer opportunities for improving cell therapy results through superior cell engraftment and liver repopulation. Ongoing clinical use of these drugs will permit rapid translation of the findings in people.

Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal injury through paracrine mechanisms.

Mesenchymal stem cells (MSCs) have been reported to preserve renal function in various models of acute kidney injury (AKI). Different routes were used to transplant MSCs but the role of cell transplantation routes in directing outcomes has been unknown. In the present study, we evaluated organ bio-distributions of transplanted MSCs, and correlated survival of transplanted cells with outcomes in mice with cisplatinum-induced AKI. We found that after intravenous administration, MSCs were largely localized in pulmonary capillaries and only a minute fraction of MSCs entered kidneys and the cells survived only transiently. Therefore, we also transplanted MSCs via intraperitoneal and renal subcapsular routes. Transplanted MSCs survived longer in peritoneal cavity and renal subcapsular space. Interestingly, when MSC transplantation was followed by cisplatinum-induced AKI, renal morphology and renal functions were better preserved, irrespective of the cell transplantation route. As transplanted MSCs did not migrate to kidneys from either peritoneal cavity or renal subcapsular space, this finding suggested that migration of cells was not required for the beneficial response. The possibility of indirect mechanisms was confirmed when administration of the conditioned medium from MSCs also protected renal tubular cells from cisplatinum-induced cytotoxicity. We identified presence of over forty regulatory cytokines in the conditioned medium obtained from MSCs. Since paracrine factors released by transplanted cells accounted for improvements, it appears that the route of cell transplantation is not critical for realizing benefits of cell therapy with MSCs in AKI. Studies of specific cytokines secreted by MSCs will help to obtain new therapeutic mechanisms for renal protection.

The relationship between ischemia-induced left ventricular dysfunction, coronary flow reserve, and coronary steal on regadenoson stress-gated (82)Rb PET myocardial perfusion imaging.

BACKGROUND: Gated rubidium-82 ((82)Rb) positron emission tomography (PET) imaging studies are acquired both at rest and during pharmacologic stress. Stress-induced ischemic left ventricular dysfunction (LVD) can produce a significant decrease in left ventricular ejection fraction (LVEF) from rest to stress. We determined the prevalence on PET of stress LVD with reduced ejection fraction (EF) and its association with absolute global and regional coronary flow reserve (CFR), and with relative perfusion defect summed difference score (SDS). METHODS AND RESULTS: We studied 205 patients with known or suspected coronary disease (120 M, 75 F, age 69 ± 13 years) who had clinically indicated rest/regadenoson stress (82)Rb PET/CT studies. Data were acquired in dynamic gated list mode. Global and 17-segment regional CFR values were computed from first-pass flow data using a 2-compartment model and factor analysis applied to auto-generated time-activity curves. Rest and stress LVEF and SDS were quantified from gated equilibrium myocardial perfusion tomograms using Emory Cardiac Toolbox software. LVD was defined as a change in LVEF of ≤-5% from rest to stress. A subgroup of 109 patients also had coronary angiography. Stress LVD developed in 32 patients (16%), with mean EF change of -10 ± 5%, vs +6 ± 7% for patients without LVD (P < .0001). EF was similar at rest in patients with and without stress LVD (57 ± 18% vs 56 ± 16%, P = .63), but lower during stress for patients with LVD (47 ± 20% vs 61 ± 16%, P = .0001). CFR was significantly lower in patients with LVD (1.61 ± 0.67 vs 2.21 ± 1.03, Wilcoxon P = .002), and correlated significantly with change in EF (r = 0.35, P < .0001), but not with SDS (r = -0.13, P = .07). The single variable most strongly associated with high risk of CAD (i.e., left main stenosis ≥50%, LAD % stenosis ≥70%, and/or 3-vessel disease) was stress EF (χ(2) = 17.3, P < .0001). There was a higher prevalence of patients with territorial CFR values ≤1.0, consistent with coronary steal, in the LVD group than in the non-LVD group (39% vs 12%, P = .001). CONCLUSIONS: LVD developed in 16% of patients undergoing (82)Rb PET myocardial perfusion imaging, and was associated with multivessel coronary artery disease. There was a significant relationship between LVD and coronary blood flow during stress, with LVD corresponding to a low CFR. Territorial CFR ≤1.0 was more common in patients with LVD than those without, suggesting that coronary steal is an important pathophysiologic mechanism contributing to pharmacologic stress-induced LVD.

Molecular Imaging of Periprosthetic Joint Infections.

Infection is an infrequent complication of lower extremity prosthetic joint surgery. Approximately one third develop within 3 months (early), another third within 1 year (delayed), and the remainder more than 1 year (late) after surgery. The diagnosis of periprosthetic joint infection is not always straightforward. Pain, the most common symptom, is present in 90%-100% of patients. The presence of fever is more variable, ranging from less than 5% to more than 40% of patients with infection. Erythema and joint swelling are often present in acute infections, but are less common in chronic infections. Erythrocyte sedimentation rate, C-reactive protein and interleukin-6 levels are useful "rule out" tests, while peripheral blood leukocyte count and serum tumor necrosis factor α are not helpful. The diagnosis of periprosthetic joint infection often requires a combination of blood, synovial fluid, and tissue sample tests, as well as imaging. Plain radiographs lack sensitivity and specificity. Molecular imaging is useful for evaluating painful joint replacements. Bone scintigraphy is most useful as a screening test. If it is negative then infection and aseptic loosening are unlikely. Combined labeled leukocyte/bone marrow imaging is a very specific test for diagnosing lower extremity joint arthroplasty infection; sensitivity is more variable. Despite more than two decades of investigation, there still is no consensus on the value of 18F-FDG for diagnosing periprosthetic joint infection. Differing test probabilities, an inability to discriminate between infection and inflammation secondary to physiologic reactions, and lack of standardized interpretative criteria are obstacles to incorporating 18F-FDG into the routine diagnostic imaging workup of periprosthetic joint infection. Preliminary results for gallium-68 citrate, fluorine-18, and technetium-99m labeled antimicrobial fragments are encouraging but no large scale trials with these agents have been conducted. Limited data suggest that labeled leukocyte/bone marrow SPECT/CT and 18F-FDG-PET/CT are specific but not sensitive for diagnosing periprosthetic infection of shoulder arthroplasties. There are minimal data on molecular imaging for monitoring treatment response in periprosthetic infections.

Imaging of Spondylodiscitis: An Update.

Spondylodiscitis is an infection of the vertebral body and/or intervertebral disc, which can also involve the epidural space, posterior elements, and paraspinal soft tissues. Due to high morbidity and mortality, prompt diagnosis and treatment of spondylodiscitis is critical. However, diagnosis can be challenging due to nonspecific signs and symptoms. Magnetic resonance imaging with and without contrast is the imaging modality of choice due to high sensitivity and specificity. Intravenous administration of gadolinium contrast can better demonstrate the extent of soft tissue and bone abscesses. However, magnetic resonance imaging is less useful in the evaluation of treatment response. When magnetic resonance imaging cannot be performed or is not diagnostic, radionuclide imaging is a useful alternative. Although bone scintigraphy frequently is used as a screening test, false negative results can occur early in the course of the infection and in the elderly. This test is not useful for detecting the soft tissue infections that often accompany or mimic spondylodiscitis. Gallium-67 citrate improves the specificity of the bone scan, can detect infection earlier than the bone scan, may be more sensitive, especially in elderly patients, and identifies accompanying soft tissue infection. Performing SPECT and SPECT/CT improve accuracy. The 2-3 day delay between radiopharmaceutical administration, poor image quality, and relatively high patient radiation dose are significant disadvantages of gallium-67. Furthermore gallium-67 is no longer as readily available as it once was. 18F-FDG imaging is the radionuclide test of choice for spondylodiscitis. The procedure, completed in one day, is sensitive, has a high negative predictive value, and reliably differentiates degenerative from infectious vertebral body end-plate abnormalities. 18F-FDG has outperformed bone and gallium-67 imaging in comparative studies. 18F-FDG may be able to provide an objective means for monitoring response to treatment. The potential of other agents for diagnosing spondylodiscitis has been studied. Although indium-111biotin accurately diagnoses spondylodiscitis, this radiopharmaceutical has never been commercially available. Gallium-68 citrate and 99mTc-radiolabeled antimicrobial peptides have been investigated, but their role in the diagnosis of spondylodiscitis has not been established. Labeled leukocyte scintigraphy has no role in the diagnosis of spondylodiscitis.

1-hour versus 3-hour 99mTc-PYP imaging to evaluate suspected cardiac transthyretin amyloidosis.

The diagnosis of cardiac transthyretin amyloidosis can involve early or delayed 99mTc-pyrophosphate planar, single photon emission computed tomography (SPECT), and/or SPECT/CT imaging. We investigated whether image interpretations differed among modalities and time points. In this observational study, data were reviewed for 173 patients with suspected transthyretin amyloidosis who underwent planar and SPECT/CT 1 and 3 hours after radiopharmaceutical injection. Planar heart-to-contralateral lung ratios were calculated. Myocardial-to-rib uptake was independently scored on SPECT and SPECT/CT as follows: 0 (negative), 1 < rib (equivocal), 2 = rib (positive), or 3 > rib (positive), and the image quality was as follows:1 (poor), 2 (adequate), and 3 (good). Three-hour SPECT/CT readings were used as the reference standard against which the other readings were compared. Twenty-five percent of patients were positive (3-hour SPECT/CT score ≥ 2). Compared to 3-hour SPECT/CT readings, there was "fair agreement" (κ = .27 - .33) with SPECT, and "fair agreement" (κ = .23 - .31) with planar imaging at 1 and 3 hours. More patients had abnormal SPECT and SPECT/CT than planar imaging (24-25% vs 16-17%, P < .007). There were more equivocal cases for 1 and 3 hours planar imaging than for 1 and 3 hours SPECT (71-73% vs 23-26%, P < .001) and 1 and 3 hours SPECT/CT (3-5%, P < .001). SPECT/CT image quality was higher at 3 hours than at 1 hour and higher than that on SPECT (P = .001). Three-hour SPECT/CT readings provided the highest number of definitive readings, had the highest image quality, and constituted the preferred protocol for evaluating unselected populations of patients that have a clinical suspicion of possible cardiac amyloidosis.

Indicators of abnormal PET coronary flow capacity in detecting cardiac ischemia.

Coronary flow capacity (CFC) categorizes severity of left ventricular (LV) ischemia by PET myocardial blood flow (MBF). Our objective was to correlate abnormal CFC with other indicators of regional ischemia. Data were examined retrospectively for 231 patients evaluated for known/suspected CAD who underwent rest and regadenoson-stress 82Rb PET/CT. MBF and myocardial flow reserve (MFR) were quantified, from which CFC was categorized as Normal CFC (1), Minimally reduced (2), Mildly reduced (3), Moderately reduced (4), and Severely reduced (5) for the three main arterial territories as well as globally. Relative perfusion summed stress score (SSS) and systolic phase contraction bandwidth (BW) were assessed. Accuracy to detect arteries with CFC ≥ 4 was highest for a Regional Index combining SSS and BW (88 ± 3%). A Global Index formed from stress ejection fraction, SSS and BW was the most accurate means of identifying patients with global CFC ≥ 4 (84 ± 3%). Arteries with abnormal CFC derived from absolute myocardial blood flow measurements are accurately identified by composite parameters combining regionally aberrant relative perfusion patterns and asynchrony.