Ultra-low-dose CT for attenuation correction: dose savings and effect on PET quantification for protocols with and without tin filter.

BACKGROUND: Ultra-low-dose (ULD) computed tomography (CT) scans should be used when CT is performed only for attenuation correction (AC) of positron emission tomography (PET) data. A tin filter can be used in addition to the standard aluminium bowtie filter to reduce CT radiation dose to patients. The aim was to determine how low CT doses can be, when utilised for PET AC, with and without the tin filter, whilst providing adequate PET quantification. METHODS: A water-filled NEMA image quality phantom was imaged in three configurations with 18F-FDG: (1) water only (0HU); (2) with cylindrical insert containing homogenous mix of sand, flour and water (SFW, approximately 475HU); (3) with cylindrical insert containing sand (approximately 1100HU). Each underwent one-bed-position (26.3 cm) PET-CT comprising 1 PET and 13 CT acquisitions. CT acquisitions with tube current modulation were performed at 120 kV/50 mAs-ref (reference standard), 100 kV/7 mAs-ref (standard ULDCT for PET AC protocol), Sn140kV (mAs range 7-50-ref) and Sn100kV (mAs range 12-400-ref). PET data were reconstructed with µ-maps provided by each CT dataset, and PET activity concentration measured in each reconstruction. Differences in CT dose length product (DLP) and PET quantification were determined relative to the reference standard. RESULTS: At each tube voltage, changes in PET quantification were greater with increasing density and reducing mAs. Compared with the reference standard, differences in PET quantification for the standard ULDCT protocol for the three phantoms were ≤ 1.7%, with the water phantom providing a DLP of 7mGy.cm. With tin filter at Sn100kV, differences in PET quantification were negligible (≤ 1.2%) for all phantoms down to 50mAs-ref, proving a DLP of 2.8mGy.cm, at 60% dose reduction compared with standard ULDCT protocol. Below 50mAs-ref, differences in PET quantification were > 2% for at least one phantom (2.3% at 25mAs-ref in SFW; 6.4% at 12mAs-ref in sand). At Sn140kV/7mAs-ref, quantification differences were ≤ 0.6% in water, giving 3.8mGy.cm DLP, but increased to > 2% at bone-equivalent densities. CONCLUSIONS: CT protocols for PET AC can provide ultra-low doses with adequate PET quantification. The tin filter can allow 60-87% lower dose than the standard ULDCT protocol for PET AC, depending on tissue density and accepted change in PET quantification.

A randomised trial of [18F]PSMA-1007-PET/CT versus NaF-PET/CT for staging primary prostate cancer: A trial protocol.

Background: Prostate-specific membrane antigen (PSMA)-positron emission tomography/contrast-enhanced computed tomography (PET/CT) is a sensitive imaging modality for prostate cancer (PCa). Due to lack of knowledge of the patient benefit, PSMA-PET/CT is not yet recommended in the European guidelines for staging and treatment planning of patients with newly diagnosed PCa. We will investigate the potential difference in progression-free survival (PFS) and quality of life (QoL) of using PSMA-PET/CT versus sodium fluoride (NaF)-PET/CT for staging and treatment planning in patients with newly diagnosed PCa. Study Design: This is a prospective randomised controlled multicentre trial carried out at three centres in the Region of Southern Denmark. Endpoints: The primary endpoint is PFS. Secondary endpoints are residual disease, stage migration, impact on treatment strategies, stage distribution, QoL and diagnostic accuracy measures. Patients and Methods: Patients eligible for the study have newly diagnosed unfavourable intermediate- or high-risk PCa. A total of 448 patients will be randomised 1:1 into two groups: (A) a control group staged with Na[18F]F-PET/CT and (B) an intervention group staged with [18F]PSMA-1007-PET/CT. A subgroup in the intervention group will have a supplementary blinded Na[18F]F-PET/CT performed for the purpose of performing accuracy analyses. QoL will be assessed at baseline and with regular intervals (3-12 months) during the study period. Treatment decisions are achieved at multidisciplinary team conferences based on the results of the respective scans and according to current Danish guidelines. Trial Registration: The Regional Committees on Health Research Ethics for Southern Denmark (S-20190161) and the Danish Medicines Agency (EudraCT Number 2021-000123-12) approved the study, and it has been registered on clinicaltrials.gov (Record 2020110469).

Observer experience and accuracy of 18F-sodium-fluoride PET/CT for the diagnosis of bone metastases in prostate cancer.

OBJECTIVE: To evaluate the diagnostic accuracy of observers with different levels of experience in reading 18F-sodium fluoride (NaF) PET/CT images for the diagnosis of bone metastases in prostate cancer (PCa) patients. METHODS: Nine observers with varying NaF PET/CT experience, ranging from no experience to 2000+ examinations, evaluated 211 NaF PET/CT scans from PCa patients participating in one of four prospective trials. Each observer evaluated each NaF PET/CT on a patient level using a trichotomous scale: M0 (no bone metastases), Me (equivocal for bone metastases) and M1 (bone metastases). Subsequently, a dichotomous evaluation was conducted (M0/M1). The final diagnosis was retrieved from the original study. For each observer, ROC curves and the diagnostic accuracy were calculated based on dichotomous and trichotomous scales; in the latter case, Me was first regarded as M1 and then M0. RESULTS: Across all experience levels, the sensitivity, specificity and accuracy using the dichotomous scale ranged from 0.81 to 0.89, 0.93 to 1.00 and 0.91 to 0.94, respectively. Employing the trichotomous scale, novice and experienced observers chose Me in up to 20 vs. 10% of cases, respectively. Considering Me as M0, the sensitivity, specificity and accuracy ranged from 0.78 to 0.89, 0.95 to 1.00 and 0.91 to 0.95, respectively. Considering Me as M1, the sensitivity, specificity and accuracy ranged from 0.86 to 0.92, 0.71 to 0.96 and 0.77 to 0.94, respectively. CONCLUSION: Novice observers used the equivocal option more frequently than observers with NaF PET/CT experience. However, on the dichotomous scale, all observers exhibited high and satisfactory accuracy for the detection of bone metastases, making NaF PET/CT an effective imaging modality even in unexperienced hands.

The diagnostic accuracy and clinical impact of FDG-PET/CT follow-up for patients on adjuvant immunotherapy for high-risk malignant melanoma.

OBJECTIVE: The benefit of FDG-PET/CT in follow-up of patients treated with adjuvant immunotherapy after resection of high-risk malignant melanoma (MM) is debated. This study evaluated the diagnostic accuracy and clinical impact of FDG-PET/CT for diagnosing MM recurrence during the first year after surgery. METHODS: We retrospectively included 124 patients with resected high-risk MM, who received adjuvant immunotherapy and follow-up FDG-PET/CT. Clinical information and AJCC-8 stage was obtained from patients' medical records. Recurrence was verified by biopsy/progression on a subsequent scan leading to change of treatment. Non-recurrence was assumed when no metastases were observed until the subsequent follow-up scan. Incidence of recurrence, sensitivity, specificity, positive and negative predictive values (PPV and NPV) were outcome measures. RESULTS: Incidence rate of MM recurrence was 0.27 [95% CI 0.17-0.37] per person-year during the first-year. Recurrence was detected in 13 patients (10%) at 3-month FDG-PET/CT, in 10 patients (8.1%) at 6 months, 1 patient (0.8%) at 9 months, 3 patients (2.4%) at 12 months. The overall sensitivity, specificity, PPV, and NPV were 97% [86-99], 82% [78-86], 39% [29-50], and 99% [98-99], respectively. The PPV trended towards higher values as disease stage increased. At the 3-month scan, the majority of actions derived from positive findings were surgery or earlier expedition of the subsequent follow-up scan. CONCLUSION: The high rate of recurrence in patients with high-risk MM treated with adjuvant immunotherapy emphasizes the need for follow-up. The potential harm by a moderately low specificity reflecting a high number of false-positive results must be weighed against the benefit of early detection of recurrence.

Lesion detection in 18F-sodium fluoride bone imaging: a comparison of attenuation-corrected versus nonattenuation-corrected PET reconstructions from modern PET-CT systems.

OBJECTIVES: An earlier study demonstrated comparable lesion detection between attenuation-corrected (AC) and nonattenuation-corrected (NAC) 18F-sodium fluoride (NaF) PET images, which is relevant for computed tomography (CT) radiation dose-saving. However, this finding may not be applicable to newer systems. The aim was to compare lesion detection between AC and NAC NaF PET images on modern PET-CT systems. METHODS: One expert and one nonexpert observer retrospectively surveyed NaF PET data in 25 breast cancer patients. At both lesion and patient level, each observer classified bone abnormalities as malignant, equivocal or benign, from NAC and AC PET images in the absence of CT. Expert interpretation of NaF PET-CT with the review of all diagnostic imaging/pathology reports for at least the subsequent 12 months provided reference standard metastases status at the patient level. Two-tailed Wilcoxon signed-rank tests measured statistically significant differences in total lesion detection between AC and NAC PET. Quadratic-weighted kappa score measured agreement in patient metastases status between observers. RESULTS: On a lesion-basis, AC PET images showed significantly more lesions than NAC for both the expert (122 versus 96; P = 0.002) and nonexpert (146 versus 132; P = 0.036) observers, with a large number of patients demonstrating disparity between AC and NAC images. For metastases status at the patient level without CT, NAC PET showed slightly better diagnostic accuracy than AC due to fewer false-positive results, as fewer lesions were identified. CONCLUSION: AC PET data provided superior lesion detection to NAC in NaF bone examinations and are thus required for clinical interpretation.

Brain glucose metabolism in patients with newly diagnosed multiple myeloma significantly decreases after high-dose chemotherapy followed by autologous stem cell transplantation.

PURPOSE: The aim of this study was to compare the effect of intensive therapy [consisting of high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT)] and conventional standard-dose chemotherapy (CDC) on brain FDG uptake, as an indicator of glucose metabolism, in multiple myeloma patients. MATERIALS AND METHODS: Twenty-four patients with newly diagnosed multiple myeloma were included. Sixteen patients received HDC/ASCT, including bortezomib-based induction therapy, and eight patients received CDC. F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT) was performed 1 and 3 hours following tracer administration before and after the treatment. The manual segmentation of supratentorial and cerebellum of each patient was performed by two independent observers. The data were expressed as global mean standardized uptake values (GSUVmean). Wilcoxon signed-rank test was used to compare changes from before to after treatment. RESULTS: A significant decrease in the GSUVmean of supratentorial brain and cerebellum was observed after treatment in the patients who received HDC/ASCT (1 hour scans: 7.03 ± 1.18 vs. 6.56 ± 0.94; P = 0.03 and 7.01 ± 1.08 vs. 6.34 ± 0.93; P = 0.01, respectively). GSUVmean changes in the patients who received CDC were not significantly different after treatment (1 hour scans: 6.47 ± 1.16 vs. 6.21 ± 0.91; P = 0.40 and 6.30 ± 1.21 vs. 6.09 ± 0.86; P = 0.62, respectively). The same findings were observed for 3 hours scans. A high level of agreement was observed between two operators. CONCLUSION: Multiple myeloma patients who received HDC/ASCT demonstrated a significant decrease in FDG uptake in the supratentorial brain and cerebellum, while patients who received CDC did not demonstrate significant changes in the brain FDG uptake.

Clinical utility of F-18 FDG PET-CT in the initial evaluation of lung cancer.

PURPOSE: Positron emission tomography-computed tomography (PET-CT) is a resource-demanding imaging modality with increasing popularity in the workup of patients with suspected or proven lung cancer. METHODS: To review the clinical usefulness of this imaging modality in the diagnosis, staging, and pre-operative evaluation, we conducted a systematic literature search, review, and quality assessment using the rapid evidence assessment toolkit and the Oxford Centre for Evidence-Based Medicine methodology. The literature search resulted in 4,208 records including 918 reviews, of which 139 met the predefined criteria and were read in full to identify relevant original articles on F-18 FDG PET-CT (1) in the evaluation of solitary pulmonary nodules (n = 14), (2) in curative-intent treatment trials (n = 9), and (3) in planning of invasive procedures (n = 18). RESULTS: We found the following important results from the literature review: 1) PET-CT can rule out malignancy in most solitary pulmonary nodules due to high sensitivity (recommendation level A). 2) PET-CT reduces the number of futile treatment trials (recommendation level A). 3) The sensitivity of PET-CT in general is insufficient to rule out mediastinal lymph node metastasis (recommendation level A). CONCLUSIONS: ᅟ 1) With few exceptions, solitary pulmonary nodules can safely be considered benign if the PET-CT scan is negative. Exceptions consist of small (<1 cm) and non-solid, solitary pulmonary nodules. These abnormalities should be followed up by CT in a structured programme. 2) No curative-intent treatment should be commenced until a PET-CT scan has excluded occult distant metastases. 3) In general, lymph node metastasis in the mediastinum cannot be ruled out on the basis of a negative PET-CT, and confirmative invasive staging should be performed in most patients before mediastinal metastasis is confirmed or ruled out.

FDG PET/CT in cancer: comparison of actual use with literature-based recommendations.

PURPOSE: The Region of Southern Denmark (RSD), covering 1.2 of Denmark's 5.6 million inhabitants, established a task force to (1) retrieve literature evidence for the clinical use of positron emission tomography (PET)/CT and provide consequent recommendations and further to (2) compare the actual use of PET/CT in the RSD with these recommendations. This article summarizes the results. METHODS: A Work Group appointed a professional Subgroup which made Clinician Groups conduct literature reviews on six selected cancers responsible for 5,768 (62.6 %) of 9,213 PET/CT scans in the RSD in 2012. Rapid Evidence Assessment was applied, using the methodology of systematic reviews with predefined limitations to search PubMed, Embase and the Cochrane Library for articles published in English/Danish/Swedish/Norwegian since 2002. PICO questions were defined, data recorded and quality appraised and rated with regard to strength and evidence level. Consequent recommendations for applications of PET/CT were established. The actual use of PET/CT was compared with these, where grades A and B indicated "established" and "useful" and grades C and D "potentially useful" and "non-recommendable" indications, respectively. RESULTS: Of 11,729 citations, 1,729 were considered for review, and 204 were included. The evidence suggested usefulness of PET/CT in lung, lymphoma, melanoma, head and neck, and colorectal cancers, whereas evidence was sparse in gynaecological cancers. The agreement between actual use of PET/CT and literature-based recommendations was high in the first five mentioned cancers in that 96.2 % of scans were made for grade A or B indications versus only 22.2 % in gynaecological cancers. CONCLUSION: Evidence-based usefulness was reported in five of six selected cancers; evidence was sparse in the sixth, gynaecological cancers. Actual use of PET/CT agreed well with recommendations.

Tumour hypoxia imaging with 18F-fluoroazomycinarabinofuranoside PET/CT in patients with locally advanced rectal cancer.

OBJECTIVE: The aim of this study was to investigate the feasibility of F-fluoroazomycinarabinofuranoside (F-FAZA) positron emission tomography (PET)/computed tomography (CT) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: The study included 14 patients with locally advanced rectal cancer. Before chemoradiotherapy, PET/CT with F-FAZA was performed with static 15 min images 2 h after injection of F-FAZA. Attenuation correction was obtained with a low-dose CT, and a contrast-enhanced CT was performed immediately after the PET scan. RESULTS: F-FAZA uptake [mean and maximum standardized uptake value (SUVmean) and (SUVmax)] was significantly higher in rectal tumours than in both muscles (P<0.003) and normal intestinal walls (P<5×10). The tumour to muscle (T/M) ratios ranged from 1.19 to 3.05 with a mean of 1.97, whereas the tumour to intestinal wall (T/I) ratios had values of 1.73-5.81 with a mean of 2.83. Intense activity accumulating in the bladder produced obvious scattered activity, which spread into the surrounding tissue. Tumour volumes excluding scatter were therefore determined, in which the SUVmax and SUVmean were also significantly higher than in both muscles (P<0.004) and normal intestinal walls (P<2×10) and had T/M ratios of 1.19-2.72 with a mean of 1.85 and T/I ratios of 1.71-5.40 with a mean of 2.67. The individual SUVmax, SUVmean, T/M and T/I values were significantly higher in the entire tumour volume compared with the tumour volume adjusted for scatter from the urinary bladder (P<0.005), although the absolute differences were small. CONCLUSION: F-FAZA PET/CT is feasible for visualization of hypoxia in patients with rectal cancer, but scattered activity from the urinary bladder should be taken into consideration.

[Chronic ischemic heart failure. Revascularization improves survival among patients with hibernating myocardium]. / Kronisk iskaemisk hjerteinsufficiens. Revaskularisering bedrer overlevelsen blandt patienter med hibernating myocardium.

INTRODUCTION: Patients with ischemic heart failure and reversible dysfunctional myocardium (Hibernating myocardium, HIB) can benefit from revascularization. These patients can be selected with nuclear methods. The purpose of this study was to describe the results of the imaging procedures in patients tested for HIB and relate the results to the choice of treatment and cause of death. MATERIALS AND METHODS: During a 2-year period 51 patients were referred to determine the amount of HIB. This can be determined with blood flow and metabolic imaging of the heart. Resting-myocardial perfusion imaging was performed with 99mTc-sestamibi and glucose metabolism was visualized with 18F-fluorodeoxyglucose (18F-FDG) gamma camera PET. Medical records and death certificate were reviewed retrospectively. RESULTS: 50 patients were included. We found an increased survival among patients with HIB who underwent revascularization (1 year mortality 6% vs. 33%, p = 0,004). Patients with HIB who did not undergo revascularization had an increased risk of sudden death. (5/15 patients vs. 0/35 patients, p = 0,003). CONCLUSION: Despite a simplified method we find the same increased mortality among medically-treated patients with HIB as in earlier studies. This and earlier studies are all retrospective with the risk of selection bias. Prospective studies are underway. Nuclear imaging is useful in evaluating patients with heart failure before revascularization.

Adaptation of nonrevascularized human hibernating and chronically stunned myocardium to long-term chronic myocardial ischemia.

It is unknown whether human chronically ischemic dysfunctional myocardium degenerates over time or adapts to chronic ischemia. We studied whether perfusion, metabolism, and contractile function and reserve can be preserved in nonrevascularized human chronically stunned and hibernating myocardium. We studied 16 event-free, medically treated patients with ejection fractions of 31 +/- 2% and chronically stunned or hibernating myocardium in 56 +/- 5% of the left ventricle on technetium-99m sestamibi single-photon emission computed tomography/fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography. Patients underwent repeat single-photon emission computed tomography, positron emission tomography, and tissue Doppler echocardiography at rest and during stress at follow-up after 25 +/- 4 months, and we investigated whether measurements of myocardial viability remained stable over time. Patients were stable with respect to New York Heart Association class and global left ventricular function (30 +/- 2%, p = 0.81). Wall motion score was unaltered in hibernating myocardium and chronically stunned regions, and a contractile reserve by tissue Doppler stress echocardiography was preserved. Overall, 74% of hibernating myocardium and chronically stunned regions retained their initial perfusion/metabolism pattern at follow-up. In hibernating myocardium, initial and follow-up sestamibi uptakes (53 +/- 1% and 53 +/- 2%, p = 0.85) and FDG uptakes (76 +/- 1% and 74 +/- 1%, p = 0.21) did not differ. In chronically stunned regions, sestamibi uptake displayed a minor decrease at follow-up (70 +/- 1% vs 67 +/- 1%, p <0.01) and FDG uptake remained constant (68 +/- 2% and 67 +/- 1%, p = 0.21). In conclusion, myocardial perfusion, FDG uptake, and contractile function in nonrevascularized chronically stunned and hibernating myocardium adapt to chronic ischemia in patients who are free of events. In chronically stunned regions, adaptation may be less complete than in hibernating myocardium.