Novel Quantitative Techniques for Assessing Regional and Global Function and Structure Based on Modern Imaging Modalities: Implications for Normal Variation, Aging and Diseased States
Section snippets
Qualitative Visual Assessment Versus Quantitation With FDG-PET
Visual assessment continues to play a pivotal role in the interpretation of PET studies. This type of interpretation is based on a contrast between the sites of uptake of radiotracer either as the result of a normal physiological process or as a result of a pathological state compared with the surrounding background. This type of assessment is particularly applicable to FDG-PET imaging in identifying regional glycolysis. With this technique, “metabolic contrast” reflects the concentration of
Quantitative Metabolic Rate Assessment and Kinetic Modeling
Quantitative kinetic analysis yields absolute rates of FDG metabolism and has the potential to measure individual rate constants, thereby providing insight into various components of glucose metabolism such as transport and phosphorylation. Advantages of this approach include availability of dynamic data and low dependency on imaging time. However, the major reason that precludes the use of full kinetic modeling in the clinical scenario is the complex and time consuming study procedure that
Nonlinear Regression Analysis
In this method, the net rate of FDG influx (Ki) can be calculated from a dynamic PET study and from a standard 2-tissue compartment model, arterial input function, and nonlinear regression analysis.1, 2, 5, 6, 7 This method, in addition to being quantitative, is independent of uptake time and provides insight into other rate constants. The usual disadvantages of a dynamic study make its implementation complex.
Patlak–Gjedde Graphical Analysis
This method originally was described by Patlak9 for a tracer that is irreversibly trapped in the tissue. With this technique, the regional concentration at time t after injection can be obtained by the following equation: where c(t) = activity in the tissue as measured by the PET scanner at time t; cp(t) = concentration of FDG in the plasma; λ = partition coefficient of FDG; Ki = net rate of FDG influx into the tissue; and T = duration of the PET scan. This method is
Standardized Uptake Value (SUV): New Concepts
Currently, SUV is the most commonly used semiquantitative parameter in clinical PET studies across the world. Several aliases such as the differential absorption ratio (DAR), differential uptake ratio (DUR), or standardized uptake ratio (SUR) have appeared from time to time in the literature as well. SUV provides a semiquantitative value and is defined as the tissue concentration of tracer, as measured by PET, divided by the injected dose normalized to patient weight multiplied by a decay
Advantages and Shortcomings of Simple SUV Measurement and Variables Affecting SUV
SUV quantitation is usually an automated procedure that is available with current software supplied with commercial PET scanners. The major advantages of SUV calculation are that it is computationally simple (with no requirement for blood sampling) and requires considerably less scanner time than the dynamic acquisition protocols. Also, the SUV of the tissue has a linear relationship with the rate of glucose metabolism as measured by kinetic modeling. Two studies11, 12 have investigated this
SUV and Body Habitus
In most programs, the SUV is normalized to patient body weight (SUVBW). Adipose tissue usually has much less metabolic activity than other tissues. Although body weight was originally used for normalization purposes (Eq. 3), later other parameters such as lean body mass (SUVLBM) and body surface area (SUVBSA) were noted to be superior14, 15, 16 compared with using body weight for accurate calculation of SUV. The latter approach reduces the variation of SUV related to the patient body
SUV and Blood Glucose Level
Serum glucose levels affect SUV measurement significantly, and many reports have demonstrated that SUVs of malignant lesions are substantially lower when FDG-PET is acquired in hyperglycemic states. In addition, hyperinsulinemia results in increased glycolysis in adipose tissue and in muscles, and therefore in low SUV measurements in other tissues. Most PET centers apply a threshold maximum plasma glucose level ranging from 150 to 200 mg/dL for examining patients before proceeding with FDG-PET.
Changes of SUV Over Time and Implications for Differentiating Benign from Malignant Lesions by Dual-Time Point Imaging
Among the various factors described previously, variations in the time interval between tracer injection and image acquisition (uptake period) substantially influence SUV. In a study by Hamberg and coworkers,20 the equilibrium time in bronchial carcinoma varied from 256 to 340 minutes after injection and decreased after therapy to 123 to 185 minutes after injection. They concluded that the time interval of 45 to 60 minutes lead to a significant underestimation of true SUV because, in most
Partial Volume Correction of SUV
The partial volume effect (PVE) is one of the important limiting technical factors for accurate quantitation with PET, mostly related to the scanner resolution. However, physiological and patient motion during data acquisition are also major factors in degrading spatial resolution, thereby also contributing to the PVE. The phenomenon is also applicable to other imaging techniques including SPECT and structural imaging, when objects with less than 2 to 3 times the spatial resolution of the
Applications in Oncology
One method to correct for the resolution effect is to use the lesion size determined on CT or MR imaging as the basis for calculating the SUV. Hickeson and coworkers41 reported an increase in accuracy from 58% to 89% by using this technique for assessing metabolic activity of lung nodules measuring less than 2 cm when a SUV threshold of 2.5 was adopted to distinguish between benign and malignant lesions (Figure 3, Figure 4, Figure 5, Figure 6). In this study, each lesion’s SUV was determined by
Advances in Medical Image Segmentation
Image segmentation, the process of identifying objects of interest in the given multidimensional image and delineating their spatial occupation in the image, has been identified as the key problem of medical image analysis, and remains a popular and challenging area of research.48 Image segmentation is increasingly used in many clinical and research applications to analyze medical imaging data sets and consists of 2 related tasks: recognition and delineation. Recognition is the process of
Concept of Global Metabolic Activity Based on Combined Structure-Function Assessment in Healthy and Diseased States
The concept of global metabolic activity was first introduced by Alavi and coworkers63 in assessment of the brain in patients with AD and in age-matched controls. These investigators were able to demonstrate that by multiplying segmented brain volumes as determined from MR images by the measured mean cerebral metabolic rates for glucose, significant differences between these two populations can be demonstrated. The same investigators have proposed adopting a similar approach for assessing
Applications of Global Metabolic Activity in Neurology
One of the major domains of neurology in which the assessment of global metabolic activity is of great interest is that of neuropsychiatric disorders. To elucidate the relationship between reduced cognitive function and cerebral metabolism in patients with AD, Alavi and coworkers63 hypothesized that the absolute amount of glucose used by the entire brain would prove to be a more reliable indicator of disease than metabolic rates calculated for a unit of brain weight alone. They investigated 20
Application of Global Metabolic Activity for Quantitation of Atherosclerosis
Bural and coworkers64 described a technique for quantitating the extent of atherosclerosis in the aorta by multiplying SUVs in the aortic wall with aortic wall volumetric data provided by CT to yield MVPs. They examined this approach in 18 patients who had both FDG-PET and contrast-enhanced CT of the chest and abdomen. All had homogeneous diffuse FDG uptake in all segments of the aortic wall. The patients were divided into 3 groups according to their age, and FDG uptake was measured in
Application of Global Metabolic Activity to Diffuse Hepatic Steatosis
Bural and coworkers47 adopted this approach to compare the FDG uptake in liver and hepatic MVPs between normal subjects and subjects with diffuse hepatic steatosis by using FDG-PET and MR imaging. They investigated 24 subjects in this study (11 men, 13 women, age range 21-75 years). All subjects had FDG -PET and MR scans within a time interval of 52 ± 60 days. Twelve of the 24 subjects had the diffuse hepatic steatosis based on MR imaging criteria. The remaining 12 were selected as age-matched
Application of Global Metabolic Activity in Oncology
Investigators from the University of Pennsylvania have examined the concept of whole body metabolic burden (WBMB) in assessing disease activity in lymphoma patients.47 Individual lesion metabolic burden (MB) was calculated by measuring the volume on CT (VCT), the mean SUV measured on PET of the CT volume (SUVmeanCT), and the recovery coefficient (RC): where RC recovers counts that extend beyond the CT volume as the result of partial volume effects and was obtained from a
Future Applications and Advances for Quantitative Imaging Techniques
The role of PET during the past decade has evolved rapidly from that of a pure research tool to a methodology of enormous importance in specialties such as oncology. FDG-PET is widely used for the diagnosis, staging, assessment of tumor response to therapy, and detection of tumor recurrence because metabolic changes usually precede changes that are associated with structural imaging alone including tumor size.
During the next few years, it is expected that sophisticated quantitative analysis
References (65)
- et al.
Mapping of functional activity in brain with 18F-fluoro-deoxyglucose
Semin Nucl Med
(1981) Calculation of cerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: A re-examination
Brain Res Rev
(1982)- et al.
Evaluation of anatomy based reconstruction for partial volume correction in brain FDG-PET
NeuroImage
(2004) - et al.
Comparative evaluation of statistical brain MR image segmentation algorithms and their impact on partial volume effect correction in PET
Neuroimage
(2006) - et al.
Interaction in the segmentation of medical images: A survey
Med Image Anal
(2001) - et al.
Role of fusion in radiotherapy treatment planning
Semin Nucl Med
(2003) - et al.
Quantitative assessment of the atherosclerotic burden of the aorta by combined FDG-PET and CT image analysis: A new concept
Nucl Med Biol
(2006) - et al.
Tumor treatment response based on visual and quantitative changes in global tumor glycolysis using PET-FDG imagingThe visual response score and the change in total lesion glycolysis
Clin Positron Imaging
(1999) - et al.
Use of 2-deoxy-D[1-11C]glucose for the determination of local cerebral glucose metabolism in humans: Variation within and between subjects
J Cereb Blood Flow Metab
(1982)
Tracer kinetic modeling in PET
The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: Theory, procedure, and normal values in the conscious and anesthetized albino rat
J Neurochem
The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man
Circ Res
Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: Validation of method
Ann Neurol
Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data
J Cereb Blood Flow Metab
Anatomy of SUV
Nucl Med Biol
[18F]fluorodeoxyglucose uptake in tumors: Kinetic vs. steady-state methods with reference to plasma insulin
J Comput Assist Tomogr
Standardized uptake value and quantification of metabolism for breast cancer imagin with FDG and L-[1-11C]tyrosine PET
J Nuc Med
SUV: Standard uptake value or silly useless value?
J Nucl Med
Stardized uptake values of FDG: Body surface area correction is preferable to body weight correction
J Nucl Med
Dependency of standardized uptake values of fluorine-18 fluorodeoxyglucose on body size: Comparison of body surface area correction and lean body mass correction
Nucl Med Commun
Solitary pulmonary nodules: Detection of malignancy with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose
Radiology
Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: Variations with body weight and a method for correction
Radiology
Breast imaging with fluorine-18-FDG PET: Quantitative image analysis
J Nucl Med
Do high glucose levels have differential effect on FDG uptake in inflammatory and malignant disorders?
Nucl Med Commun
The dose uptake ratio as an index of glucose metabolism: Useful parameter or oversimplification?
J Nucl Med
FDG uptake at extended time periods in non small cell cancer—Implications for improved cancer management
J Nucl Med
Dual time point fluorine-18 fluorodeoxyglucose positron emission tomography: A potential method to differentiate malignancy from inflammation and normal tissue in the head and neck
Eur J Nucl Med
Dual time point 18F-FDG PET for the evaluation of pulmonary nodules
J Nucl Med
Optimal scan time for fluorine-18 fluorodeoxyglucose positron emission tomography in breast cancer
Eur J Nucl Med
Potential of dual-time-point imaging to improve breast cancer diagnosis with 18F-FDG PET
J Nucl Med
Dual time point 18F-FDG PET imaging detects breast cancer with high sensitivity and correlates well with histologic subtypes
J Nucl Med
Cited by (98)
Ustekinumab treatment is associated with decreased systemic and vascular inflammation in patients with moderate-to-severe psoriasis: Feasibility study using <sup>18</sup> F-fluorodeoxyglucose PET/CT
2019, Journal of the American Academy of DermatologyMolecular imaging of β-cells: diabetes and beyond
2019, Advanced Drug Delivery ReviewsNovel Quantitative PET Techniques for Clinical Decision Support in Oncology
2018, Seminars in Nuclear MedicineThe Role of PET in Evaluating Atherosclerosis: A Critical Review
2018, Seminars in Nuclear Medicine