Novel Quantitative Techniques for Assessing Regional and Global Function and Structure Based on Modern Imaging Modalities: Implications for Normal Variation, Aging and Diseased States

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In this review, we describe the current approaches used for quantitative assessment of regional and global function with positron emission tomography (PET) imaging (combined with structural imaging modalities) with emphasis on both research and clinical applications of this powerful approach. We particularly refer to the impact of such measurements in assessing physiological processes such as aging and measuring response to treatment in serious disorders such as cancer. Although a multitude of methods has been described in literature, the optimal approaches that are both accurate and practical in clinical settings need to be defined and refined. Standardized uptake value (SUV) continues to be the most widely used index in the current practice. Calculating SUV at a single time point and assigning standard regions of interest are inadequate and suboptimal for the purposes adopted by the medical community. The concepts of partial volume correction for measured values in small lesions, dual-time point and delayed PET imaging, and global metabolic activity for assessment of various stages of disease may overcome deficiencies that are associated with the current quantitative (ie, SUV) techniques. Serious consideration of these concepts will enhance the role and reliability of these quantitative techniques, and therefore compliment the World Health Organization or the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for managing patients with cancer and other disorders, including physiological states such as aging and serious diseases such as atherosclerosis and neurological diseases. We also introduce the concepts that allow for segmentation of various structural components of organs like the brain for accurate measurement of functional parameters. We also describe complicated kinetic modeling and methodologies that have been used frequently for assessing metabolic and pharmacological parameters in the brain and other organs. Simplified quantitative techniques based on these concepts are described, but should be validated against the kinetic models to test their role as practical tools.

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:c(t)=λcp(t)+Ki0Tcp(t)dt 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):MB=SUVmeanCT(VCT)/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)

  • R. Carson

    Tracer kinetic modeling in PET

  • L. Sokoloff et al.

    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

    (1977)
  • M. Reivich et al.

    The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man

    Circ Res

    (1979)
  • M.E. Phelps et al.

    Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: Validation of method

    Ann Neurol

    (1979)
  • C.S. Patlak et al.

    Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data

    J Cereb Blood Flow Metab

    (1983)
  • S.-C. Huang

    Anatomy of SUV

    Nucl Med Biol

    (2000)
  • H. Minn et al.

    [18F]fluorodeoxyglucose uptake in tumors: Kinetic vs. steady-state methods with reference to plasma insulin

    J Comput Assist Tomogr

    (1993)
  • A. Kole et al.

    Standardized uptake value and quantification of metabolism for breast cancer imagin with FDG and L-[1-11C]tyrosine PET

    J Nuc Med

    (1997)
  • J. Keyes

    SUV: Standard uptake value or silly useless value?

    J Nucl Med

    (1995)
  • C.K. Kim et al.

    Stardized uptake values of FDG: Body surface area correction is preferable to body weight correction

    J Nucl Med

    (1994)
  • C.K. Kim et al.

    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

    (1996)
  • N. Gupta et al.

    Solitary pulmonary nodules: Detection of malignancy with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose

    Radiology

    (1992)
  • K.R. Zasadny et al.

    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

    (1993)
  • N. Avril et al.

    Breast imaging with fluorine-18-FDG PET: Quantitative image analysis

    J Nucl Med

    (1997)
  • H.M. Zhuang et al.

    Do high glucose levels have differential effect on FDG uptake in inflammatory and malignant disorders?

    Nucl Med Commun

    (2001)
  • L.M. Hamberg et al.

    The dose uptake ratio as an index of glucose metabolism: Useful parameter or oversimplification?

    J Nucl Med

    (1994)
  • J.W. Kung et al.

    FDG uptake at extended time periods in non small cell cancer—Implications for improved cancer management

    J Nucl Med

    (2004)
  • R. Hustinx et al.

    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

    (1999)
  • A. Matthies et al.

    Dual time point 18F-FDG PET for the evaluation of pulmonary nodules

    J Nucl Med

    (2002)
  • A.R. Boerner et al.

    Optimal scan time for fluorine-18 fluorodeoxyglucose positron emission tomography in breast cancer

    Eur J Nucl Med

    (1999)
  • R. Kumar et al.

    Potential of dual-time-point imaging to improve breast cancer diagnosis with 18F-FDG PET

    J Nucl Med

    (2005)
  • A. Mavi et al.

    Dual time point 18F-FDG PET imaging detects breast cancer with high sensitivity and correlates well with histologic subtypes

    J Nucl Med

    (2006)
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