Calculation Of Standardized Uptake Values Research Articles

Calculation of standardized uptake values (SUVs) and time activity curves (TACs) of mice in FDG-PET

Abstract Positron Emission Tomography (PET) with 18Ffluorodeoxyglucose (FDG) is an important imaging practice in cancer diagnosis, staging, treatment planning, and response assessment. Accurate interpretation of PET results requires an understanding of FDG uptake in organs. The time activity curve (TAC) and standardized uptake value (SUV) are the two common tools to measure tracer uptake in regions of interest. The TAC provides information on glucose consumption dynamics, while the SUV involves measuring the amount of tracer taken up by a specific region or volume of interest, and then adjusting the measurement by the amount of tracer injected and the subject’s characteristics. In the current study, we measured the TACs and SUVs of the heart, brain, kidney, and muscle in ten mice injected with FDG over a period of 120 minutes. According to the TACs obtained in this study, the brain has a slower uptake than the other organs with a tendency to keep the FDG for a longer period of time. Also, the SUV of the brain showed a rising trend until the middle of the experiment with a sharp falloff afterwards. The pattern of the curves of the other three organs was almost the same. The findings of this study were in agreement with a similar study on humans and are explained by the metabolic activity and physiology of the organs studied.

U-Net-based SUV calculation in FDG-PET imaging of mice brain for enhanced analysis

Abstract Positron emission tomography (PET) is a widely used imaging modality in nuclear medicine for a variety of applications. Amongst the methods used for the quantifying and interpretation of PET images, the standardized uptake value (SUV) is a widely-adopted semi-quantitative tool that supplements visual understanding with quantitative information. SUV is used in both clinical and preclinical practices to report the status of various normal organs and tumors under investigation using PET imaging. While the determination of SUVs is typically done manually, which can be tedious, artificial intelligence (AI) can be utilized to enhance the efficiency of the process. In this study, a U-Net-based approach was employed for semi-automated determination of SUV in FDG-PET scans of mice brains. First, a U-Net model was trained using 50 FDG-PET images of six mice to perform the automatic segmentation task. The trained model then delineated the brain of a mouse which was then processed by a short in-house code to extract data and calculate the SUV. The process was also replicated in a manual way for comparison purposes. The comparison of the results from the U-Net-based segmentation method and the conventional manual method at nine different time points revealed that there were errors of less than 4.5% in eight out of the nine-time points. Although our U-Net model’s performance needs improvement, adapting a well-trained AIbased approach for SUV determination, particularly in preclinical studies, can help reduce the workload of organ delineation and minimize associated errors, facilitating SUV determination.

Analysis of quantitative [I-123] mIBG SPECT/CT in a phantom and in patients with neuroblastoma

PurposeTo determine the accuracy of quantitative SPECT, intersystem and interpatient standardized uptake value (SUV) calculation consistency for a manufacturer-independent quantitative SPECT/CT reconstruction algorithm, and the range of SUVs of normal and neoplastic tissue.MethodsA NEMA body phantom with 6 spheres (ranging 10–37 mm) was filled with a known activity-to-volume ratio and used to determine the contrast recovery coefficient (CRC) for each visible sphere, and the measured SUV accuracy of those spheres and background water solution. One hundred eleven 123I-metaiodobenzylguanidine ([I-123] mIBG) SPECT/CT examinations from 43 patients were reconstructed using SUV SPECT® (HERMES Medical Solutions Inc.); 42 examinations were acquired using a GE Infinia Hawkeye 4 SPECT/CT, and 69 were acquired on a Siemens Symbia Intevo SPECT/CT. Inter scanner SUV analysis of 9 regions of normal [I-123] mIBG tissue uptake was conducted. Intrapatient mean SUV variability was calculated by measuring normal liver uptake within patients scanned on both cameras. The intensity of uptake by neoplastic tissue in the images was quantified using maximum SUV and, if present, compared over time.ResultsThe phantom results of the visible spheres and background resulted in accuracy calculations better than 5–10% with CRC correction. Interscanner SUV variability showed no statistical difference (average p value 0.559; range 0.066–1.0) among the 9 normal tissues analyzed. Intrapatient liver mean SUV varied ≤ 16% as calculated for 28 patients (87 examinations) studied on both scanners. In one patient, a thoracic tumor evaluated over 10 time points (18 months) underwent a 74% (3.1/12.0) reduction in maximum SUV with treatment.ConclusionThe results demonstrate quantitative accuracy to better than 10%, and both consistent SUV calculation between 2 different SPECT/CT scanners for 9 tissues, and low intrapatient measurement variability for quantitative SPECT/CT analysis in a pediatric population with neuroblastoma. Quantitative SPECT/CT offers the opportunity for objective analysis of tumor response using [I-123] mIBG by normalizing the uptake to injected dose and patient weight, as is done for PET.

Tissue standardized uptake value is a closer surrogate of blood fluorine-18 fluorodeoxyglucose clearance after division by blood standardized uptake value, illustrated in brain and liver

The numerator and denominator of the left-hand side of the Gjedde-Patlak-Rutland (GPR) equation for measurement of blood fluorine-18 fluorodeoxyglucose (F-FDG) clearance into tissue (Ki) are the standardized uptake values (SUVs) of tissue and blood, respectively. The extent to which normalized time (NT) in the GPR equation exceeds real time depends on half-time of clearance of F-FDG from blood. A literature review shows that NT is fairly constant, about 100 min at 60 min postinjection of F-FDG, in keeping with our own finding of no significant difference in maximum SUV in blood 60 min postinjection of F-FDG between 39 patients with F-FDG-avid malignancy on routine PET/CT (1.74±0.31) and 21 patients with normal PET/CT (1.79±0.32), and similar blood glucose levels (BGLs). Volume of distribution (V0) in the GPR equation is ∼0.4 ml/ml for brain and ∼0.9 ml/ml for lean liver. Using these values of V0 and an NT of 100 min, we used the GPR equation to calculate Ki from our own published values of SUVliver/SUVblood and SUVbrain/SUVblood at 60 min postinjection, obtaining 0.0045 ml/min/ml for liver and 0.036 ml/min/ml for brain at BGL of 5 mmol/l. These values for Ki at this BGL are close to literature values of Ki, which for liver and brain are ∼0.0033 and ∼0.035 ml/min/ml, respectively. We conclude, therefore, that following division with blood pool SUV, tissue SUV becomes a closer surrogate of Ki. This division also eliminates the controversy over which whole body metric to use in the calculation of SUV.

SUV calculation in breast cancer: which normalization should be applied when using 18F-FDG PET?

When using 18F-FDG PET, glucose metabolism quantification is affected by various factors. We aimed to investigate the benefit of different standardized uptake value (SUV) normalizations to improve the accuracy of 18F-FDG uptake to predict breast cancer aggressiveness and response to treatment. Two hundred fifty-two women with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC) were included. Women underwent 18F-FDG PET before and after the first course of NAC. Glucose serum levels, patient heights and weights were recorded at the time of each PET exam. Four different procedures for SUV normalization of the primary tumor were used: by body weight (SUVBW) by blood glucose level (SUVG), by lean body mass (SUL) and then corrected for both lean body mass and blood glucose level (SULG). At baseline, SUL was significantly lower than SUVBW (5.9±4.0 and 9.5±6.5, respectively; P<0.0001), whereas SUVG and SUVBW were not significantly different (9.7±6.4 and 9.5±6.5, respectively; P=0.67). Concerning SUV changes (ΔSUV), the different normalizations methods did not induce significant quantitative differences. The correlation coefficients were high between the four normalizations methods of SUV1, SUV2 and ΔSUVB (R>0.95; P<0.0001). High baseline SUVBW measures were positively correlated with the biological tumor characteristics of aggressiveness and proliferation (P<0.001): ductal carcinoma, high tumor grading, high mitotic activity, negative estrogen receptor status and the TNBC subtype. ΔSUVBW was highly predictive of pCR (AUC=0.76 on ROC curve analysis; P<0.0001). The different SUV normalizations yields identical statistical results and AUC to predict tumor biological aggressiveness and response to therapy. In the present setting, SUVBW and SUL can be considered as robust measures and be used in future multicenter trials. The additional normalization of SUV by glycemia involves stringent methodologic procedures to avoid biased risk measurements and offers no statistical advantages.

Digital Imaging and Communications in Medicine (DICOM) information conversion procedure for SUV calculation of PET scanners with different DICOM header information

PurposeIn nuclear medicine, the standardized uptake value (SUV) obtained using positron emission tomography with 2-deoxy-2-fluoro-D-glucose (FDG-PET) is widely used as a semi-quantitative diagnosis factor. We found that the header file of the Philips Allegro PET scanner using the Digital Imaging and Communications in Medicine (DICOM) standard was stored differently than with other scanners. Thus, the purpose of this study was to develop a DICOM header information conversion program to ensure compatibility between Allegro and other equipment. Methods and resultsThe NEMA IEC Body phantom was scanned using the Allegro PET scanner. We conducted measurements and performed calculations by using commercial software and the proposed self-developed program, respectively, to compare the SUVs by using conversion data. The program consists of three parts: an input part that can load data regardless of the number of DICOM images, and conversion and output parts that can be used to convert the DICOM header information and store it in the order of slices. The results of the calculation are in good agreement with the data measured at 12 circular regions of interest. The percent difference was lower than the 20%. ConclusionIn conclusion, this study suggested a simple and convenient method to solve the incompatibility through conversion of the DICOM header information. This study thus provides physicians more accurate information for diagnosis and treatment.

AB1007 Increased Vascular Wall Inflammation in Patients with Active Rheumatoid Arthritis as Measured by an 18F-Fdg-Pet/Ct Scan

BackgroundPatients with rheumatoid arthritis (RA) have an elevated risk of developing cardiovascular disease (CVD). Like active RA, atherosclerosis is an inflammatory process. There are indications that aortic inflammation in atherosclerosis...

Repeatable Noninvasive Measurement of Mouse Myocardial Glucose Uptake with 18F-FDG: Evaluation of Tracer Kinetics in a Type 1 Diabetes Model

A noninvasive and repeatable method for assessing mouse myocardial glucose uptake with (18)F-FDG PET and Patlak kinetic analysis was systematically assessed using the vena cava image-derived blood input function (IDIF). Contrast CT and computer modeling was used to determine the vena cava recovery coefficient. Vena cava IDIF (n = 7) was compared with the left ventricular cavity IDIF, with blood and liver activity measured ex vivo at 60 min. The test-retest repeatability (n = 9) of Patlak influx constant K(i) at 10-40 min was assessed quantitatively using Bland-Altman analysis. Myocardial glucose uptake rates (rMGU) using the vena cava IDIF were calculated at baseline (n = 8), after induction of type 1 diabetes (streptozotocin [50 mg/kg] intraperitoneally, 5 d), and after acute insulin stimulation (0.08 mU/kg of body weight intraperitoneally). These changes were analyzed with a standardized uptake value calculation at 20 and 40 min after injection to correlate to the Patlak time interval. The proximal mouse vena cava diameter was 2.54 ± 0.30 mm. The estimated recovery coefficient, calculated using nonlinear image reconstruction, decreased from 0.76 initially (time 0 to peak activity) to 0.61 for the duration of the scan. There was a 17% difference in the image-derived vena cava blood activity at 60 min, compared with the ex vivo blood activity measured in the γ-counter. The coefficient of variability for Patlak K(i) values between mice was found to be 23% with the proposed method, compared with 51% when using the left ventricular cavity IDIF (P < 0.05). No significant bias in K(i) was found between repeated scans with a coefficient of repeatability of 0.16 mL/min/g. Calculated rMGU values were reduced by 60% in type 1 diabetic mice from baseline scans (P < 0.03, ANOVA), with a subsequent increase of 40% to a level not significantly different from baseline after acute insulin treatment. These results were confirmed with a standardized uptake value measured at 20 and 40 min. The mouse vena cava IDIF provides repeatable assessment of the blood time-activity curve for Patlak kinetic modeling of rMGU. An expected significant reduction in myocardial glucose uptake was demonstrated in a type 1 diabetic mouse model, with significant recovery after acute insulin treatment, using a mouse vena cava IDIF approach.

Variation in urinary excretion of FDG, yet another uncertainty in quantitative PET

BackgroundThe standardized uptake value (SUV) is the most common estimate of metabolic activity used in clinical positron emission tomography (PET). Several biological and technological factors influence the accurate SUV calculation.PurposeTo assess another potential source of variability of the SUV, the variations in urinary excretion of fluorodeoxyglucose (FDG).Material and MethodsTwenty patients with various malignancies scheduled for PET/CT with 18F-FDG were included in the present study. The activity in urine voided immediately before image acquisition was measured and decay corrected. An estimation of FDG content in the urinary bladder was made during imaging, and the two components of urinary FDG were added. The urinary output of FDG, and the quantity of FDG divided by the time to measurements, was estimated.ResultsThe excretion of FDG in urine was between 5.7% and 15.2% of injected dose (decay corrected), and from 0.06% to 0.3%/min after injection, a five-fold difference in clearance.ConclusionAbout 10% of injected dose is excreted in urine at 70 min post injection, but the urinary FDG excretion was found to be highly variable, yet another uncertainty affecting the SUV measurements.

PET-MRI in the head and neck area: challenges and new directions

In the March 2011 number of European Radiology, Boss and co-authors describe their first experiences with the feasibility of simultaneous PET-MR imaging in the head and upper neck area [1]. They found that simultaneous PETMRI of head and neck cancer was feasible with a new hybrid PET-MRI prototype, using a removable brain PETdetector that can be placed within the MR gantry. They report that MRI datasets acquired during simultaneous PET data acquisition exhibited excellent image quality without any recognisable artefacts or distortions caused by the PET insert. PET datasets showed slight streak artefacts, which did not lead to degradation of tumour visualization. Images obtained with the PET-MRI system exhibited better detailed resolution and greater image contrast in comparison to those from the PET-CT system. The authors also report that full quantification of regional radiotracer activity is not yet possible. This precludes the calculation of standardized uptake values as a semi-quantitative measure of radiotracer accumulation and local uptake needs to be scaled towards a reference tissue. The authors state that this current deficit is expected to be amended soon by implementing a calibration workflow. A clear disadvantage of this PET-MRI system mainly designed for brain imaging is the small field-ofview of the PET component of approximately 19 cm. Therefore the axial field of view of the PET insert typically reached to structures located cranially of the angle of the mandible, leaving the larynx and hypopharyx outside the fieldof-view. Actually the authors only report on nasopharyngeal and not even on oral and oropharyngeal carcinomas. Magnetic resonance imaging provides unmatched soft tissue detail along with a reasonable array of functional information through techniques as MRI diffusion and MRI perfusion. However it will take a long time before MRI can provide the molecular detail that PET does and PET provides the anatomical information that MRI does, so a combination of the two technologies is the most reasonable option. Combining the two advanced imaging technologies without degrading the original optimum performance of either is challenging [2]. At present, three solutions are considered by manufacturers: a sequential, insert and integrated approach. In the sequential construct, the PET and MRI systems are placed in a sequence. This approach is used in PET-CT and most currently available PET-MRI. However, multimodality imaging performed with separate imaging devices requires patients repositioning, which results in a greater risk of voluntary or involuntary patient movements between procedures. There are some physiologic processes such as tissue perfusion, which may change rapidly over time that consecutive data acquisition of PET and MRI may yield inaccurate results and a fully integrated system for simultaneous data acquisition is necessary. In the long term it remains to be determined if PET-MRI set-ups with sequential data acquisition capacity have a future because, especially in the mobile head and neck, there will be problems regarding reposition. In addition the options for optimizing workflow are restricted. The insert construct system involves building a removable PET-detector that can be placed within the MR gantry. The study in the article under discussion made use of this combination: a brain PET in a slightly modified clinical 3.0 J. A. Castelijns (*) Department of Radiology, VU University Medical Center, De Boelelaan 1117, 1081 HVAmsterdam, The Netherlands e-mail: j.castelijns@vumc.nl

Individualized quantification of brain β-amyloid burden: results of a proof of mechanism phase 0 florbetaben PET trial in patients with Alzheimer’s disease and healthy controls

Complementing clinical findings with those generated by biomarkers--such as β-amyloid-targeted positron emission tomography (PET) imaging--has been proposed as a means of increasing overall accuracy in the diagnosis of Alzheimer's disease (AD). Florbetaben ([(18)F]BAY 94-9172) is a novel β-amyloid PET tracer currently in global clinical development. We present the results of a proof of mechanism study in which the diagnostic efficacy, pharmacokinetics, safety and tolerability of florbetaben were assessed. The value of various quantitative parameters derived from the PET scans as potential surrogate markers of cognitive decline was also investigated. Ten patients with mild-moderate probable AD (DSM-IV and NINCDS-ADRDA criteria) and ten age-matched (≥ 55 years) healthy controls (HCs) were administered a single dose of 300 MBq florbetaben, which contained a tracer mass dose of < 5 μg. The 70-90 min post-injection brain PET data were visually analysed by three blinded experts. Quantitative assessment was also performed via MRI-based, anatomical sampling of predefined volumes of interest (VOI) and subsequent calculation of standardized uptake value (SUV) ratios (SUVRs, cerebellar cortex as reference region). Furthermore, single-case, voxelwise analysis was used to calculate individual "whole brain β-amyloid load". Visual analysis of the PET data revealed nine of the ten AD, but only one of the ten HC brains to be β-amyloid positive (p = 0.001), with high inter-reader agreement (weighted kappa ≥ 0.88). When compared to HCs, the neocortical SUVRs were significantly higher in the ADs (with descending order of effect size) in frontal cortex, lateral temporal cortex, occipital cortex, anterior and posterior cingulate cortices, and parietal cortex (p = 0.003-0.010). Voxel-based group comparison confirmed these differences. Amongst the PET-derived parameters, the Statistical Parametric Mapping-based whole brain β-amyloid load yielded the closest correlation with the Mini-Mental State Examination scores (r = -0.736, p < 0.001), following a nonlinear regression curve. No serious adverse events or other safety concerns were seen. These results indicate florbetaben to be a safe and efficacious β-amyloid-targeted tracer with favourable brain kinetics. Subjects with AD could be easily differentiated from HCs by both visual and quantitative assessment of the PET data. The operator-independent, voxel-based analysis yielded whole brain β-amyloid load which appeared valuable as a surrogate marker of disease severity.

Breast cancer with low FDG uptake: characterization by means of dual-time-point FDG-PET/CT

Malignant breast lesions usually are differentiated by FDG-PET with a semiquantitative FDG standardized uptake value (SUV) of 2.5. However, the frequency of breast cancer with an SUV of less than or equal to 2.5 is noteworthy and often presents diagnostic challenges. This study was undertaken to evaluate the accuracy of dual-time-point FDG-PET/CT with FDG SUV calculation in the characterization of such breast tumors.

Quality Assurance of Positron Emission Tomography/Computed Tomography for Radiation Therapy

Recent advances in radiation delivery techniques, such as intensity-modulated radiation therapy, provide unprecedented ability to exquisitely control three-dimensional dose distribution. Development of on-board imaging and other image-guidance methods significantly improved our ability to better target a radiation beam to the tumor volume. However, in reality, accurate definition of the location and boundary of the tumor target is still problematic. Biologic and physiologic imaging promises to solve the problem in a fundamental way and has a more and more important role in patient staging, treatment planning, and therapeutic assessment in radiation therapy clinics. The last decade witnessed a dramatic increase in the use of positron emission tomography and computed tomography in radiotherapy practice. To ensure safe and effective use of nuclide imaging, a rigorous quality assurance (QA) protocol of the imaging tools and integration of the imaging data must be in place. The application of nuclide imaging in radiation oncology occurs at different levels of sophistication. Quantitative use of the imaging data in treatment planning through image registration and standardized uptake value calculation is often involved. Thus, QA should not be limited to the performance of the scanner, but should also include the process of implementing image data in treatment planning, such as data transfer, image registration, and quantitation of data for delineation of tumors and sensitive structures. This presentation discusses various aspects of nuclide imaging as applied to radiotherapy and describes the QA procedures necessary for the success of biologic image-guided radiation therapy.

Deep-Inspiration Breath-Hold PET/CT: Clinical Findings with a New Technique for Detection and Characterization of Thoracic Lesions

Respiratory motion during PET/CT acquisition can cause misregistration and inaccuracies in calculation of standardized uptake values (SUVs). Our aim was to compare the detection and characterization of thoracic lesions on PET/CT with and without a deep-inspiration protocol. We studied 15 patients with suspected pulmonary lesions who underwent clinical PET/CT, followed by deep-inspiration breath-hold (BH) PET/CT. In BH CT, the whole chest of the patient was scanned in 15 s at the end of deep inspiration. For BH PET, patients were asked to hold their breath 9 times for 20-s intervals. One radiologist reviewed images, aiming to detect and characterize pulmonary, nodal, and skeletal abnormalities. Clinical CT and BH CT were compared for number, size, and location of lesions. Lesion SUVs were compared between clinical PET and BH PET. Images were also visually assessed for accuracy of fusion and registration. All patients had lesions on clinical CT and BH CT. Pulmonary BH CT detected more lesions than clinical CT in 13 of 15 patients (86.7%). The total number of lung lesions detected increased from 53 with clinical CT to 82 with BH CT (P<0.001). Eleven patients showed a total of 31 lesions with abnormal (18)F-FDG uptake. BH PET/CT had the advantage of reducing misregistration and permitted a better localization of sites with (18)F-FDG uptake. A higher SUV was noted in 22 of 31 lesions on BH PET compared with clinical PET, with an average increase in SUV of 14%. BH PET/CT enabled an increased detection and better characterization of thoracic lesions compared with a standard PET/CT protocol, in addition to more precise localization and quantification of the findings. The technique is easy to implement in clinical practice and requires only a minor increase in the examination time.

Molecular Imaging of Proliferation in Malignant Lymphoma

We have determined the ability of positron emission tomography (PET) with the thymidine analogue 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) to detect manifestation sites of malignant lymphoma, to assess proliferative activity, and to differentiate aggressive from indolent tumors. In this prospective study, FLT-PET was done additionally to routine staging procedures in 34 patients with malignant lymphoma. Sixty minutes after i.v. injection of approximately 330 MBq FLT, emission and transmission scanning was done. Tracer uptake in lymphoma was evaluated semiquantitatively by calculation of standardized uptake values (SUV) and correlated to tumor grading and proliferation fraction as determined by Ki-67 immunohistochemistry. FLT-PET detected a total of 490 lesions compared with 420 lesions revealed by routine staging. In 11 patients with indolent lymphoma, mean FLT-SUV in biopsied lesions was 2.3 (range, 1.2-4.5). In 21 patients with aggressive lymphoma, a significantly higher FLT uptake was observed (mean FLT-SUV, 5.9; range, 3.2-9.2; P < 0.0001) and a cutoff value of SUV = 3 accurately discriminated between indolent and aggressive lymphoma. Linear regression analysis indicated significant correlation of FLT uptake in biopsied lesions and proliferation fraction (r = 0.84; P < 0.0001). In this clinical study, FLT-PET was suitable for imaging malignant lymphoma and noninvasive assessment of tumor grading. Due to specific imaging of proliferation, FLT may be a superior PET tracer for detection of malignant lymphoma in organs with high physiologic fluorodeoxyglucose uptake and early detection of progression to a more aggressive histology or potential transformation.

A threshold method to improve standardized uptake value reproducibility

Although standardized uptake values (SUV) are widely used to quantify the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours, there are systematic differences in the way this index is applied by different investigators. The aims of this study were to compare the effects of using maximum or mean region counts in the calculation of SUV and to investigate an alternative technique based on a fixed fraction of the maximum counts. Simulated PET projections of the thorax were generated together with spherical lesions that varied in diameter from 1.6 to 4.8 cm with uptake values of 2, 4 and 8. The lesion SUVs were determined using either the maximum (SUVmax) or mean count (SUVmean) values found in regions circumscribing the lesion. In addition, average values were calculated that only included region pixels that exceeded a selected fraction of maximum value (SUV0.6max or SUV0.75max). These methods were also applied to six clinical 18F-FDG PET studies with a total of 12 lesions. The SUVs for these lesions were determined independently by four observers. Decreases with respect to SUVmax of 57%, 23% and 14% were found for SUVmean, SUV0.6max and SUV0.75max approaches respectively in the simulation study. The variation in SUVmean with region size was 35%, while the SUV0.6max and SUV0.75max was less than 3%. Similar results were obtained for the clinical data. We conclude that the proposed technique produces SUVs that are essentially independent of lesion region size and shape. It is expected that this will provide a more stable and reliable result than current approaches.