Association between body mass index (BMI) and [123I]Ioflupane (DaTSCAN) availabilities in patients with parkinsonism using single-photon emission computed tomography-computed tomography (SPECT-CT).

AIM: [123I]Ioflupane (DaTSCAN) has a high binding affinity to the dopamine (DA) transporter (DaT) and tenfold less affinity to serotonin (5-HT) transporter (SERT). Both neurotransmitters are considered to contribute to body weight regulation. This study assesses the association between body mass index (BMI) and DaTSCAN availability in brain. METHOD: Scans from 74 consecutive patients who had undergone DaTSCAN single-photon emission computed tomography-computed tomography (SPECT-CT) were used to obtain semi- and absolute quantitative data in several volumes of interest (VOIs). Relative semi-quantitative specific binding ratios (SBRs) from Chang attenuated SPECT were obtained from GE DaTQUANT. Absolute normalised concentration (NC) was calculated from attenuation/scatter corrected SPECT-CT images, using an adapted version of the EARL Ltd (European Association of Nuclear Medicine (EANM) Research 4 Life) template. Scans were subdivided into either degenerative parkinsonism (abnormal = 49), borderline (n = 14) or scan without evidence of dopaminergic deficit (SWEDD = 11) using visual assessment and SBR values by two nuclear medicine consultants. RESULTS: SBRs did not correlate with BMI. However, NC values correlated negatively in the entire cohort, with the strongest correlation in the frontal (r = - 0.649. p = 0.000), occipital (r = - 0.555, p = 0.000) regions and pons (r = - 0.555, p = 0.000). In the abnormal (n = 49) and SWEDD group (n = 11), NC of the frontal region was the most correlated with BMI (r = - 0.570, p = 0.000; r = - 0.813, p = 0.002, respectively). In the borderline group (n = 14), the left posterior putamen displayed the strongest correlation (r = - 0.765, p = 0.001). CONCLUSION: Absolute NC values demonstrate a strong inverse correlation with BMI, strongest in the extrastriatal regions. Due to the predominately non-overlapping distribution of DaT and SERT, this study suggests greater involvement of SERT in obesity with possible interplay with DA transmission.

Quantitative lymphoscintigraphy of the lower limbs for the diagnosis of phlebolymphoedema.

INTRODUCTION: Phlebolymphoedema is caused by the interaction of the venous and lymphatic systems in a state of chronic venous insufficiency in which increased microvascular filtration causes an increased rate of lymph production. Lymphatic drainage rate increases in response, but this is unsustainable and can cause lymphatic failure and oedema. We hypothesise that in phlebolymphoedema we could measure unusually high lymphatic drainage while the lymph system is still fully functional. METHOD: Patients referred for lymphoscintigraphic investigation of swollen legs between April 2021 and December 2022 were reviewed. Quantitative lymphoscintigraphy was performed following the technique of Keramida et al . (2017) and ilio-inguinal nodal uptake (IIQ%) was calculated. The presence of scintigraphic features of increased lymph production was noted for each limb. RESULTS: A total of 39 patients were reviewed (78 limbs, 29F, 10M). Seven limbs were identified with supranormal lymphatic function (IIQ > 30%) plus three borderline. Of these 10 limbs, all had at least two scintigraphic features of increased lymph production. CONCLUSION: Quantitative lymphoscintigraphy, although developed for diagnosing abnormally low lymphatic function, may also have utility at the upper end of the spectrum for identifying chronic venous insufficiency. An IIQ% upper normal limit of 30% could be used to diagnose venous insufficiency as the cause for limb swelling. This is of note for patients of large body habitus in whom venous ultrasound is difficult.

Quantitative [123]I-Ioflupane DaTSCAN single-photon computed tomography-computed tomography in Parkinsonism.

AIM: [123]I-Ioflupane (DaTSCAN) binds to the presynaptic dopamine transporter (DAT) and with a lower affinity to the serotonin transporter (SERT). We aimed to develop a novel method to quantify absolute uptake in the striatal (predominantly DAT binding) and extra-striatal regions (mainly SERT binding) using single-photon computed tomography-computed tomography (SPECT-CT) DaTSCAN and to improve DaTSCAN image quality. METHOD: Twenty-six patients with Parkinsonism underwent DaTSCAN SPECT-CT prospectively. The scans were visually analyzed independently by two experienced reporters. Specific binding ratios (SBRs) from Chang attenuation corrected SPECT were obtained using GE DaTQuant. Normalized concentrations and specific uptakes (NSU) from measured attenuation and modelled scatter-corrected SPECT-CT were obtained using HERMES Hybrid Recon and Affinity and modified EARL volumes of interest. RESULTS: Striatal NSU and SBR positively correlate ( R  = 0.65-0.88, P  = 0.00). SBR, normalized concentrations, and NSU box plots differentiated between scans without evidence of dopaminergic deficit and abnormal scans. Interestingly, body weight inversely correlated with normalized concentrations values in extra-striatal regions [frontal ( R  = 0.81, P  = 0.00); thalamus ( R  = 0.58, P  = 0.00); occipital ( R  = 0.69, P  = 0.00)] and both caudate nuclei [ R  = 0.42, P  = 0.03 (Right), R  = 0.52, P  = 0.01 (Left)]. Both reporters noted improved visual quality of SPECT-CT versus SPECT images for all scans. CONCLUSION: DaTSCAN SPECT-CT resulted in more accurate quantification, improved image quality, and enabled absolute quantification of extra-striatal regions. More extensive studies are required to establish the full value of absolute quantification for diagnosis and monitoring the progression of neurodegenerative disease, to assess an interplay between DAT and SERT, and to verify whether serotonin and DATs are potentially dysfunctional in obesity.

Artificial Intelligence in Nuclear Medicine: Opportunities, Challenges, and Responsibilities Toward a Trustworthy Ecosystem.

Trustworthiness is a core tenet of medicine. The patient-physician relationship is evolving from a dyad to a broader ecosystem of health care. With the emergence of artificial intelligence (AI) in medicine, the elements of trust must be revisited. We envision a road map for the establishment of trustworthy AI ecosystems in nuclear medicine. In this report, AI is contextualized in the history of technologic revolutions. Opportunities for AI applications in nuclear medicine related to diagnosis, therapy, and workflow efficiency, as well as emerging challenges and critical responsibilities, are discussed. Establishing and maintaining leadership in AI require a concerted effort to promote the rational and safe deployment of this innovative technology by engaging patients, nuclear medicine physicians, scientists, technologists, and referring providers, among other stakeholders, while protecting our patients and society. This strategic plan was prepared by the AI task force of the Society of Nuclear Medicine and Molecular Imaging.

Tailoring the sampling time of single-sample GFR measurement according to expected renal function: a multisite audit.

BACKGROUND: The 2018 BNMS Glomerular Filtration Rate (GFR) guidelines recommend a single-sample technique with the sampling time dictated by the expected renal function, but this is not known with any accuracy before the test. We aimed to assess whether the sampling regime suggested in the guidelines is optimal and determine the error in GFR result if the sample time is chosen incorrectly. We can then infer the degree of flexibility in the sampling regime. METHODS: Data from 6328 patients referred for GFR assessment at 6 different hospitals for a variety of indications were reviewed. The difference between the single-sample (Fleming) GFR result at each sample time and the slope-intercept GFR result at each hospital was calculated. A second dataset of 777 studies from one hospital with nine samples collected from 5 min to 8 h post-injection was analysed to provide a reference GFR to which the single-sample results were compared. RESULTS: Recommended single-sample times have been revised: for an expected GFR above 90 ml/min/1.73m2 a 2-h sample is recommended; between 50 and 90 ml/min/1.73m2 a 3-h sample is recommended; and between 30 and 50 ml/min/1.73m2 a 4-h sample is recommended. Root mean square error in single-sample GFR result compared with slope-intercept can be kept less than or equal to 3.30 ml/min/1.73m2 by following these recommendations. CONCLUSION: The results of this multisite study demonstrate a reassuringly wide range of sample times for an acceptably accurate single-sample GFR result. Modified recommended single-sample times have been proposed in line with the results, and a lookup table has been produced of rms errors across the full range of GFR results for the three sample times which can be used for error reporting of a mistimed sample.

Accuracy of next-day single-sample measurement for low glomerular filtration rate and comparison with same-day slope-intercept glomerular filtration rate.

AIM: We aimed to investigate the accuracy of a single-sample glomerular filtration rate (SS-GFR) technique with a sample taken at 24 h post-injection for patients with GFR lower than 25 mL/min/1.73 m2. A comparison with the results from same-day slope-intercept GFR (SI-GFR) was also performed. METHODS: Data from patients referred for GFR assessment to inform the management of chronic kidney disease at the Royal Free Hospital were reviewed. Four-sample SI-GFR calculation with samples at 2-, 4-, 6-, and 24-h post-injection was taken as the reference measurement to which the Gref and Karp SS-GFR (24-h sample) and same-day SI-GFR (2- and 4-h samples) were compared. The effect of protein binding on GFR accuracy was modelled. RESULTS: A total of 43 GFR examinations with reference GFR less than 25 mL/min/1.73 m2 were included in the analysis. Bland-Altman analysis gave mean differences of 0.4 mL/min/1.73 m2 (95% confidence interval: 0-0.7) for SS-GFR (24 h) and 3.0 mL/min/1.73 m2 (95% confidence interval: 1.9-4.2) for same-day SI-GFR. 95% limits of agreement were -2.0 to 2.8 mL/min/1.73 m2 for SS-GFR (24 h) and -4.0 to 10.1 mL/min/1.73 m2 for same-day SI-GFR. CONCLUSIONS: SS-GFR with a 24-h sample is more accurate than same-day SI-GFR in patients with GFR less than 25 mL/min/1.73 m2. Using SS-GFR with a 24-h sample in routine clinical practice will result in clinically insignificant differences in GFR result compared with the reference technique, whereas a same-day SI-GFR measurement could cause large inaccuracies.

Correction of slope-intercept glomerular filtration rate measurement without scaling for body size.

AIM: The aim of this study was to evaluate a slope-intercept glomerular filtration rate (GFR) one-compartment correction method based exclusively on the rate constant (α2) of the exponential between 2 and 4 h post-injection that requires no scaling for BSA. METHODS: The correction factor is 1/([C.α2]+1). C depends on the difference between one-compartment-corrected and uncorrected GFR, so varies with different correction procedures. Patients were in four groups: group 1 (Cr-EDTA; n = 141) and group 2 (Tc-DTPA; n = 47) had sampling at 2, 3 and 4 h. Groups 3A (Tc-DTPA; n = 168) and 3B (Tc-DTPA; n = 361) gave nine samples up to 480 min. C was calculated from GFR corrected using Brochner-Mortensen (BM) without prior BSA-scaling (CBM; GFRBM), after BSA-scaling then reverse-scaling as per British Nuclear Medicine Society (BNMS) guidelines (CBNMS; GFRBNMS), and after correction using the equations containing 'f' described by Fleming (CFlem; GFRFlem) and Jodal and Brochner-Mortensen (CJBM; GFRJBM). In group 3A, C (C9) was determined from GFR measured from all nine samples (GFR9) and from seven samples (C7) up to 240 min. In 3B, GFRC, corrected using 1/([C9.α2]+1), was compared with GFRBM, GFRBNMS, GFRFlem and GFRJBM against GFR9 (gold-standard). RESULTS: C derived from these one-compartment correction formulae ranged from 25 to 32 min. In group 3, C7 and C9 were 28 ± 11 and 38 ± 14 min (P < 0.0001). Biases of GFRBM, GFRBNMS, GFRJBM, GFRFlem and GFRC against GFR9 were 2.7, 1.5, 4.2, 3.4 and 0.4 ml/min. Corresponding precisions were 9.3, 7.3, 7.0, 6.7 and 7.6 ml/min. CONCLUSION: Correction using α2 avoids BSA scaling, has a low bias against gold-standard GFR and does not over-correct at high GFR.

99mTc DTPA vs. 51Cr EDTA for glomerular filtration rate measurement: is there a systematic difference?

AIM: The study aimed to investigate whether a systematic difference exists between Cr EDTA and Tc DTPA for measurement of glomerular filtration rate (GFR). METHODS: The distribution of GFR results from candidates attending the Royal Free Hospital for assessment of suitability for kidney donation was compared before and after the change from Cr EDTA to Tc DTPA using three-sample slope-intercept GFR calculation with samples at 2, 3, and 4 hours. A second cohort of oncology patients attending Leeds Teaching Hospitals NHS Trust underwent simultaneous GFR measurement with both tracers by full characterisation of the plasma clearance curve with nine samples between 5 minutes and 8 hours post-injection. Three-sample slope-intercept GFR was also calculated for comparison with cohort 1. RESULTS: From the first cohort, a statistically significant (P = 0.008) systematic difference of 5.8% (95% confidence interval: 1.5%-10.1%) was found in the three-sample slope-intercept GFR, with Tc DTPA giving the higher result. From the second cohort, a statistically significant (P = 0.00001) systematic difference of 2.9% (95% confidence interval: 1.8%-3.9%) was found in three-sample slope-intercept GFR, with Tc DTPA giving the higher result. There was no statistically significant difference between the tracers when GFR was calculated by full characterisation of the plasma clearance curve. CONCLUSION: There is a small systematic difference between GFR measured with Tc DTPA and Cr EDTA using abbreviated techniques, which is removed when GFR is calculated by full characterisation of the plasma clearance curve. The difference is not clinically significant in the context of intra-patient variability of GFR measurement.

Patient-specific optimisation of administered activity and acquisition times for 18F-FDG PET imaging.

BACKGROUND: The purpose of this study is to identify a method for optimising the administered activity and acquisition time for 18F-FDG PET imaging, yielding images of consistent quality for patients with varying body sizes and compositions, while limiting radiation doses to patients and staff. Patients referred for FDG scans had bioimpedance measurements. They were injected with 3 MBq/kg of 18F up to 370 MBq and scanned on a Siemens Biograph mCT at 3 or 4 min per bed position. Data were rebinned to simulate 2- and 1-min acquisitions. Subjective assessments of image quality made by an experienced physician were compared with objective measurements based on signal-to-noise ratio and noise equivalent counts (NEC). A target objective measure of image quality was identified. The activity and acquisition time required to achieve this were calculated for each subject. Multiple regression analysis was used to identify expressions for the activity and acquisition time required in terms of easily measurable patient characteristics. RESULTS: One hundred and eleven patients were recruited, and subjective and objective assessments of image quality were compared for 321 full and reduced time scans. NEC-per-metre was identified as the objective measure which best correlated with the subjective assessment (Spearman rank correlation coefficient 0.77) and the best discriminator for images with a subjective assessment of "definitely adequate" (area under the ROC curve 0.94). A target of 37 Mcount/m was identified. Expressions were identified in terms of patient sex, height and weight for the activity and acquisition time required to achieve this target. Including measurements of body composition in these expressions was not useful. Using these expressions would reduce the mean activity administered to this patient group by 66 MBq compared to the current protocol. CONCLUSIONS: Expressions have been identified for the activity and acquisition times required to achieve consistent image quality in FDG imaging with reduced patient and staff doses. These expressions might need to be adapted for other systems and reconstruction protocols.

Incidence of a single subsegmental mismatched perfusion defect in single-photon emission computed tomography and planar ventilation/perfusion scans.

OBJECTIVE: This study aims to compare the incidence of ventilation/perfusion (V/Q) scans interpreted as indeterminate for the diagnosis of pulmonary embolism (PE) using single-photon emission computed tomography (SPECT) versus planar scintigraphy and to consider the effect of variable interpretation of single subsegmental V/Q mismatch (SSM). METHODS: A total of 1300 consecutive V/Q scans were retrospectively reviewed. After exclusion and matching for age and sex, 542 SPECT and 589 planar scans were included in the analysis. European Association of Nuclear Medicine guidelines were used to interpret the V/Q scans, initially interpreting SSM as negative scans. Patients with SSM were followed up for 3 months and further imaging for PE was collected. RESULTS: Indeterminate scans were significantly fewer in the SPECT than the planar group on the basis of the initial report (7.7 vs. 12.2%, P<0.05). This is irrespective of classification of SSM as a negative scan (4.6 vs. 12.1%, P<0.0001) or an indeterminate scan (8.3 vs. 12.2%, P<0.05). Of the 21 patients who had SSM, 19 underwent computer tomography pulmonary angiogram and embolism was found in one patient. None of these patients died at the 3-month follow-up. CONCLUSION: V/Q SPECT has greater diagnostic certainty of PE, with a 41% reduction in an indeterminate scan compared with planar scintigraphy. This is irrespective of the clinician's interpretation of SSM as negative or intermediate probability. Patients with SSM would not require further computer tomography pulmonary angiogram imaging.

The significance of incidental brain uptake on 68Ga-DOTATATE PET-CT in neuroendocrine tumour patients.

OBJECTIVE: Radiolabelled somatostatin analogues detect neuroendocrine tumours (NETs), but may reveal other tumour types. We examined the prevalence of possible meningioma in patients with known or suspected NETs imaged with Ga-DOTATATE PET-computed tomography (CT) on the basis of central nervous system uptake and compared with findings on magnetic resonance and contrast-enhanced CT imaging. METHODS: Retrospective imaging reports from 313 patients who had undergone Ga-DOTATATE PET imaging for primary or repeat NET staging were searched to identify suspected meningiomas on PET. Images were then compared with findings on subsequent complementary MRI or contrast-enhanced CT scanning (performed within mean±112 days of PET-CT) if available. RESULTS: Of 313 patients, 22 had regions of uptake suggestive of meningioma. MRI was available for 12 patients and contrast-enhanced CT was available for one patient. Of these, one patient with known von Hippel-Lindau syndrome had probable cerebellar NET metastasis. Six patient scans indicated lesions consistent with PET. Two of these reported initially did not comment on meningioma. No obvious lesion was found in the remaining six patients; however, five showed a possible correlation to venous structures. The mean maximum standardized uptake value±SEM for lesions in all 21 probable meningioma patients was 4.90±0.45. CONCLUSION: Ga-DOTATATE is a sensitive marker of probable meningioma and may identify small lesions not reported on subsequent MRI. Lesions clearly observed on PET were identified on review in half of patients where complementary MR or CT imaging was available. Haemangioblastoma and metastatic NETs may have focal peripheral uptake similar to meningioma on Ga-DOTATATE PET and should be considered in the differential.

Radiation dose of 18F-FDG to lactating breasts, its effect on the effective dose and a more accurate effective dose from 18F-FDG.

INTRODUCTION: Lactating breasts have greater uptake of fluorine-18 fluorodeoxyglucose (F-FDG) than nonlactating breasts; however, there are no published data on the radiation dose from F-FDG to lactating breasts or this effect on the effective dose (ED). In addition, the International Commission on Radiological Protection's (ICRP) most recently published ED of 1.9×10 mSv/MBq from F-FDG was calculated using weighting factors that have since been superseded. We therefore calculated the F-FDG radiation dose to the lactating breast, its effect on the ED and calculated more up-to-date EDs from F-FDG for nonlactating patients. METHODS: Breast uptake of F-FDG and volume were determined from PET/CT images of a lactating patient. These data, together with previously published biokinetic data on F-FDG, were used to calculate a radiation dose to the lactating breasts and its effect on the ED. In addition, tissue weighting factors and organ doses from the ICRP publications 103 and 106 were used to calculate more up-to-date EDs from F-FDG in nonlactating patients. RESULTS: The absorbed dose to the lactating breast from F-FDG is 1.75×10 mGy/MBq, which results in an increase in the ED of 6%. In nonlactating patients, a more up-to-date ED from F-FDG is 1.77×10 mSv/MBq for women and 1.64×10 mSv/MBq for men. CONCLUSION: This is the first reported dosimetry of F-FDG in lactating breasts, data that are required when justifying the radiation dose from an F-FDG PET scan in lactating patients. In addition, we calculated more up-to-date EDs from F-FDG that are lower than the current widely reported ED and should be used in future publications on F-FDG.

Effectiveness of quality control methods for glomerular filtration rate calculation.

PURPOSE: In this work, we aimed to identify the types of errors encountered in glomerular filtration rate (GFR) measurement and test the effectiveness of all published quality control (QC) methods for detection of clinically significant errors. METHODS: A total of 412 GFR tests were carried out on adults and children. The three-point slope-intercept glomerular filtration rate (SI-GFR) was compared with the nine-point 'area under curve' calculation as a gold standard to determine the error in SI-GFR. The Durbin-Watson test was used to characterize the nature of the errors. The sensitivity, specificity and positive predictive value (PPV) of QC methods for detecting clinically significant errors were calculated and receiver operating characteristic curves were constructed. The QC methods were also applied to a dataset of 100 four-point GFR tests from different institutions. RESULTS: Model failure is the dominant cause of clinically significant error in this dataset, with individual point measurement errors only giving rise to clinically significant errors in a small number of cases. No QC test had an acceptable combination of sensitivity, PPV and specificity. The correlation coefficient QC test had the largest area under the receiver operating characteristic curve (0.73). No other QC test had an area greater than 0.57. CONCLUSION: All the QC methods have poor sensitivity and PPV for detecting clinically significant errors and so cannot be relied on to ensure a robust measurement of GFR, underlining the need for careful working practices and a thorough system of measurement checks. We found no evidence for the value of multiple sampling with respect to QC; until such evidence is published, their clinical utility is unproven.

A systematic review of single-sample glomerular filtration rate measurement techniques and demonstration of equal accuracy to slope-intercept methods.

PURPOSE: We aimed to identify the most accurate single-sample glomerular filtration rate (SS-GFR) technique for all patient ages. MATERIALS AND METHODS: We performed a systematic review of all published SS-GFR measurement techniques and compared the results from each test with a gold-standard nine-point 'area-under-curve' measurement of GFR as well as slope-intercept (SI-GFR) methods for 412 GFR tests. RESULTS: We have shown that for patients of all ages the SS-GFR technique developed by Fleming and colleagues delivers the best accuracy and precision, with results equivalent to those calculated by SI-GFR. The median percentage difference from the gold-standard GFR for the Fleming technique is 4.8% (95% confidence interval 3.9-5.7%) and that for the three-point SI-GFR is 5.6% (95% confidence interval 4.9-6.3%). The interquartile range of the distribution of percentage difference from the gold standard is -0.23 to 11% for the Fleming method and 1.6-11% for the three-point SI-GFR. CONCLUSION: The Fleming technique outperforms the method currently recommended by the international guidelines, and is simpler as only one equation is required for all patients instead of separate equations for adults and children. We propose that the SS-GFR technique of Fleming replace the methods currently recommended by the international and BNMS guidelines for routine measurement of GFR for expected results greater than 30 ml/min/1.73 m. A thorough system of measurement checks should be implemented for all methods of GFR assessment; the perceived lack of opportunity for quality control checks to be performed on the result of a single-sample measurement is addressed in the companion paper of this study.

Validation and impact of a new technique for assessment of glomerular filtration rate in patients with liver disease.

OBJECTIVES: Previously we have proposed a technique for the measurement of plasma clearance in patients with ascites. The impact of using the technique was assessed and the results compared with those from a reference technique in 111 patients having glomerular filtration rate measurements as part of their workup for liver transplantation. METHODS: Results of calculations using the new technique were compared with plasma clearance measurements obtained using a conventional slope-intercept technique and with clearance measurements based on urine collection. Discrepancies between the results of plasma clearance and urinary clearance assessments were investigated by using an uncollimated gamma camera to measure the total retention of the tracer. RESULTS: Conventional slope-intercept calculations overestimated clearance compared with the new technique by more than 20% in 21% of the patients. Significant differences between the results of the two methods were more likely in patients with more severe ascites. Results of urine collection-based measurements of Cr-51 EDTA clearance were frequently significantly lower than measurements using the new technique, whereas measurements of urinary clearance of creatinine were higher. Gamma camera measurements suggest that discrepancies between total and urinary clearance of Cr-51 EDTA are due to incomplete urine collection. CONCLUSION: The new technique is a practical method for assessment of kidney function and should be used in patients with liver disease who have or may have ascites.