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.

ACR Appropriateness Criteria® Imaging After Total Hip Arthroplasty.

This article reviews evidence for performing various imaging studies in patients with total hip prostheses. Routine follow-up is generally performed with radiography. Radiographs are also usually the initial imaging modality for patients with symptoms related to the prosthesis. Following acute injury with pain, noncontrast CT may add information to radiographic examination regarding the presence and location of a fracture, component stability, and bone stock. Image-guided joint aspiration, noncontrast MRI, and white blood cell scan and sulfur colloid scan of the hip, are usually appropriate studies for patients suspected of having periprosthetic infection. For evaluation of component loosening, wear, and/or osteolysis, noncontrast CT or MRI are usually appropriate studies. Noncontrast MRI is usually appropriate for identifying adverse reaction to metal debris related to metal-on-metal articulations. For assessing patients after hip arthroplasty, who have trochanteric pain and nondiagnostic radiographs, ultrasound, or MRI are usually appropriate studies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

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.

Appearance of aseptic vascular grafts after endovascular aortic repair on [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography.

BACKGROUND: Diagnosis of prosthetic vascular graft infection with [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) allows for early detection of functional changes associated with infection, based on increased glucose utilization by activated macrophages and granulocytes. Aseptic vascular grafts, like all foreign bodies, can stimulate an inflammatory response, which can present as increased activity on 18F-FDG PET/CT. Consequently, distinguishing aseptic inflammation from graft infection, though important, can be difficult. In the case of endovascular aneurysm repair (EVAR), a minimally invasive procedure involving the transfemoral insertion of an endoprosthetic stent graft, the normal postoperative appearance of these grafts on 18F-FDG PET/CT can vary over time, potentially confounding study interpretation. AIM: To investigate the visual, semiquantitative, and temporal characteristics of aseptic vascular grafts in patients status post EVAR. METHODS: In this observational retrospective cohort study, patients with history of EVAR who underwent 18F-FDG PET/CT for indications other than infection were identified retrospectively. All patients were asymptomatic for graft infection - no abdominal pain, fever of unknown origin, sepsis, or leukocytosis - at the time of imaging and for ≥ 2 mo after each PET/CT. Imaging studies such as CT for each patient were also reviewed, and any patients with suspected or confirmed vascular graft infection were excluded. One hundred two scans performed on 43 patients (34 males; 9 females; age = 77 ± 8 years at the time of the final PET/CT) were retrospectively reviewed. All 43 patients had an abdominal aortic (AA) vascular graft, 40 patients had a right iliac (RI) limb graft, and 41 patients had a left iliac (LI) limb graft. Twenty-two patients had 1 PET/CT and 21 patients had from 2 to 9 PET/CTs. Grafts were imaged between 2 mo to 168 mo (about 14 years) post placement. Eight grafts were imaged within 6 mo of placement, including three that were imaged within three months of placement. The mean interval between graft placement and PET/CT for all 102 scans was 51 ± 39 mo. PET/CT data was reconstructed with region-of-interest analysis of proximal, mid and distal portions of the grafts and background ascending aorta. Maximum standardized uptake value (SUVmax) was recorded for each region. SUVmax-to-background uptake ratios (URs) were calculated. Visual assessment was performed using a 2-pattern grading scale: Diffuse (homogeneous uptake less than liver uptake) and focal (one or more areas of focal uptake in any part of the graft). Statistical analysis was performed. RESULTS: In total, there were 306 AA grafts, 285 LI grafts, 282 RI grafts, and 306 ascending aorta background SUVmax measurements. For all 102 scans, mean SUVmax values for AA grafts were 2.8-3.0 along proximal, mid, and distal segments. Mean SUVmax values for LI grafts and RI grafts were 2.7-2.8. Mean SUVmax values for background were 2.5 ± 0.5. Mean URs were 1.1-1.2. Visual analysis of the scans reflected results of quantitative analysis. On visual inspection, 98% revealed diffuse, homogeneous 18F-FDG uptake less than liver. Graft URs and visual pattern categories were significantly associated for AA graft URs (F-ratio = 21.5, P < 0.001), LI graft URs (F-ratio = 20.4, P < 0.001), and RI graft URs (F-ratio = 30.4, P < 0.001). Thus, visual patterns of 18F-FDG uptake corresponded statistically significantly to semiquantitative URs. The age of grafts showing focal patterns was greater than grafts showing diffuse patterns, 87 ± 89 vs 50 ± 37 mo, respectively (P = 0.02). URs were significantly associated with graft age for AA grafts (r = 0.19, P = 0.001). URs were also significantly associated with graft age for LI grafts (r = 0.25, P < 0.0001), and RI grafts (r = 0.31, P < 0.001). Quartiles of similar numbers of graft (n = 25-27) grouped by graft age indicated that URs were significantly higher for 4th quartile vs 2nd quartile URs (F-ratio = 19.5, P < 0.001). When evaluating URs, graft SUVmax values within 10%-20% of the ascending aorta SUVmax is evident in aseptic grafts, except for grafts in the oldest quartiles. In this study, grafts in the oldest quartiles (> 7 years post EVAR) showed SUVmax up to 30% higher than the ascending aorta SUVmax. CONCLUSION: Characteristics of an aseptic vascular stent graft in the aorta and iliac vessels on 18F-FDG PET/CT include graft SUVmax values within 10%-20% of the ascending aorta background SUVmax. The SUVmax of older aseptic grafts can be as much as 30% above background. The visual uptake pattern of diffuse, homogeneous uptake less than liver was seen in 98% of aseptic vascular grafts, making this pattern particularly reassuring for clinicians.

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.

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.

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.

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.

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.

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.

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.

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.

Comparison and validation of automated scoring of SPECT phantom cold rod visibility.

PURPOSE: Evaluation of phantom image quality is an integral component of the quality assurance of SPECT systems. This evaluation often is done by visual assessment of the resolution of known structures of a specified size, such as arrays of cold rods in a warm background. Although this method is rapid and convenient, it is qualitative and is subject to inter- and intraobserver variability. Thus an automated quantitative analysis would be preferable. Several metrics of cold rod visibility have been developed, although their suitability for SPECT quality assurance depends on how well they correspond to visual scoring by experienced observers. METHODS: Various metrics of cold rod visibility, derived from either texture analysis or template-based analysis, were investigated. The texture analysis methods measured the normalized gray-level co-occurrence matrix (GLCM) energy ("Energy%") and entropy ("Entropy%") of each region and an associated combination of the two ("EnergyEntropy%"). One template-based method measured the rods-to-background contrast ("Contrast") and an associated visibility index (Contrast × area = "Contrast Visibility"). Another template-based method performed binary classification (BC) of the rods and background to compute the area under curve (AUC) of its receiver operating characteristics (ROC) curve ("BC-AUC") and the corresponding signal-to-noise ratio ("BC-SNR"). All these metrics were computed for 90 SPECT acquisitions of the standard American College of Radiology ("Jaszczak") phantom. Cold rod visibility was scored independently by two experienced nuclear medicine physicists on both dichotomous and 5-point scales. Scoring was performed twice by each observer to evaluate variability. RESULTS: Interobserver agreement (Cohen's kappa statistic) was 0.78, and intraobserver reproducibility was 0.86 and 0.88, respectively, for each observer. Mean and median scores differed significantly between observers. Accuracy of each metric was assessed according to AUC of ROC analysis with respect to mean dichotomous score. The binary classification metrics had the highest accuracy (BC-AUC = 0.995, BC-SNR = 0.994), above that of the texture analysis metrics (Entropy% = 0.992, Energy% = 0.988, EnergyEntropy% = 0.992) and conventional template analysis (Contrast = 0.984, Contrast Visibility = 0.989). The metrics were similar in terms of rank correlation to mean visibility score. BC-AUC correlated linearly with mean visibility score (R2  = 0.95) and consistently performed among the highest of the metrics vs rod diameter and count level. CONCLUSIONS: Automated quantitative analysis of SPECT phantom cold rods correlated well with visual scoring. The metrics based on binary classification performed particularly well for this task, across the range of rod diameters and count levels. The suboptimal interobserver agreement highlights the importance of developing automated algorithms for evaluating scanner performance.

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.

A pilot study treatment of malignant tumors using low-dose 18F-fluorodeoxyglucose (18F-FDG).

Photons, electrons and protons have therapeutic use however positrons have only been used for diagnostic imaging purposes. The energies of positrons (ß+) from F-18 (0.633 MeV) and electrons (ß-) from I-131 (0.606 MeV) are very close and have similar equilibrium dose constants. Since [18F]-fluorodeoxyglucose (18F-FDG) clears rapidly from circulation, administration of 37-74 GBq (1-2 Ci) of 18F-FDG is relatively safe from an internal radiation dosimetry point of view. We initiated a phase I dose escalation study to assess the safety, toxicity, and potential therapeutic utility of administering 100-200 mCi/m2 18F-FDG delivered over a 1 to 5 day period in patients with advanced lymphomas and solid tumors refractory to standard of care treatment (SCT). Here we report the results of the first four patients treated. Four patients with advanced cancers received a single dose of 3.7-7.4 GBq/m2 (100-200 mCi/m2) 18F-FDG. We monitored the patients for adverse effects and for response. No treatment-related toxicities were observed. There was no increased radiation exposure to personnel. Two patients showed decrease in the index lesions' SUVs by 17-33% (Day 1) and 25-31% (Day 30) post treatment. The two other patients showed stable disease on 18F-PET-CT. Interestingly, responses were seen at low radiotherapy doses (below 1 Gy). This exploratory study demonstrated the safety of therapeutic administration of up to 14.2 GBq (385 mCi) 18F-FDG. In patients with 18F-FDG-avid cancers, targeted radionuclide 18F-FDG therapy appears safe and may offer clinical benefit.