Advanced intra-tumoural structural characterisation of hepatocellular carcinoma utilising FDG-PET/CT: a comparative study of radiomics and metabolic features in 3D and 2D.

PURPOSE: The aim of our work is to evaluate the correlation of two-dimensional (2D) and three-dimensional (3D) radiomics and metabolic features of hepatocellular carcinoma (HCC) with tumour diameter, staging, and metabolic tumour volume (MTV). MATERIAL AND METHODS: Thirty-three patients with HCC were studied using 18F-fluorodeoxyglucose positron-emission tomography with computed tomography (18F [FDG] PET/CT). The tumours were segmented from the PET images after CT correction. Metabolic parameters and 35 radiomics features were compared using 2D and 3D modes. The metabolic parameters and tumour morphology were compared using 2 different types of software. Tumour heterogeneity was studied in both metabolic parameters and radiomics features. Finally, the correlation between the metabolic and radiomics features in 3D mode, as well as tumour morphology and staging according to the American Joint Committee on Cancer (AJCC) staging were studied. RESULTS: Most of the metabolic parameters and radiomics features are statically stable through the 2D and 3D modes. Most of the 3D mode features show a correlation with metabolic parameters; the total lesion glycolysis (TLG) shows the highest correlation, with a Spearman correlation coefficient (rs) of 0.9776. Also, the grey level run length matrix/run length non-uniformity (GLRLM_RLNU) from radiomics features exhibits a correlation with a Spearman correlation coefficient of 0.9733. Maximum tumour diameter is correlated with TLG and GLRLM_RLNU, with rs equal to 0.7461 and 0.7143, respectively. Regarding AJCC staging, some features show a medium but prognostic correlation. In the case of 2D-mode features, all metabolic and radiomics features show no significant correlation with MTV, AJCC staging, and tumour maximum diameter. CONCLUSIONS: Most of the normal metabolic parameters and radiomics features are statistically stable through the 3D and 2D modes. 3D radiomics features are significantly correlated with tumour volume, maximum diameter, and staging. Conversely, 2D features have negligible correlation with the same parameters. Therefore, 3D mode features are preferable and can accurately evaluate tumour heterogeneity.

Comparison of atherosclerotic inflammation and calcification in subjects with end stage renal disease (ESRD) on hemodialysis to normal controls utilizing 18F-FDG PET/CT.

OBJECTIVE: Subjects with end stage renal disease (ESRD) are exposed to increased morbidity and mortality due to cardiovascular events. The primary underlying mechanism has been suggested as accelerated atherosclerosis in these patients. Our aim was to compare the atherosclerotic inflammation and calcification in subjects with ESRD on hemodialysis to that in normal controls utilizing fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT). SUBJECTS AND METHODS: Forthy two subjects who underwent 18F-FDG PET/CT imaging were retrospectively studied. Twenty one were subjects with ESRD on hemodialysis (67±11 years old; 14 male, 7 female) and 21 were age- and gender-matched controls. Average standardized uptake value maximum (SUVmax) and SUVmean for 4 segments of the aorta (ascending, arch, descending, abdominal) and for the common iliac arteries and common femoral arteries were measured. Standardized uptake value maximum and SUVmean for right atrial blood pool were also measured as the background. Average SUVmax, average SUVmean, average SUVmax/background ratio, and average SUVmean/background ratio were compared between subject groups for all segments. Presence or absence of macroscopic calcification on CT images for each arterial segment based on visual qualitative assessment was also noted and compared. For statistical analysis, two-sided t-test was used for continuous variables, and chi-square test was used for categorical variables. We considered a P value of <0.05 as statistically significant. RESULTS: Average SUVmax and SUVmean were statistically significantly greater in subjects with ESRD than in controls in all arterial segments. Average SUVmax/background ratios were statistically significantly greater in subjects with ESRD compared to normal controls in all arterial segments except for the left femoral artery. Average SUVmean/background ratios were statistically significantly greater in subjects with ESRD compared to normal controls in all arterial segments except for the right and left femoral arteries. Presence of calcification on CT was more frequently encountered in all arterial segments in subjects with ESRD, and was statistically significantly greater for the aortic arch, descending aorta, and right and left femoral arteries. CONCLUSION: SUV measurements representing the atherosclerotic inflammatory changes and macroscopic atherosclerotic calcifications appear to be accelerated in subjects with ESRD on hemodialysis compared to normal controls. Fluorine-18 FDG PET/CT is a valuable diagnostic tool for verifying and quantifying accelerated atherosclerosis secondary to ESRD.

Is 18F-FDG PET/CT a valuable diagnostic tool for verifying accelerated atherosclerosis secondary to diabetes mellitus on insulin in the aortic segments and large arteries?

OBJECTIVE: Fluorine-18 fluorodeoxylglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has a well-established role for detection and quantification of atherosclerotic inflammatory disease using standardized uptake value (SUV) measurements. Our aim was to compare the inflammatory and macroscopic calcification processes of atherosclerosis in the aortic segments and large arteries of subjects with insulin dependent diametes mellitus (IDDM) compared to those of age-matched controls via 18F-FDG PET/CT. PATIENTS AND METHODS: A hundred and ten subjects who underwent 18F-FDG PET/CT imaging for oncological diseases were retrospectively studied. Fifty five were diabetics on insulin and 55 were age-matched controls. Average SUVmax and SUVmean for four segments of aorta and for common iliac arteries and femoral arteries were measured and compared between subject groups. Presence or absence of macroscopic calcification on CT images for each arterial segment was also noted and compared between these groups. RESULTS: Average SUVmax and SUVmean were statistically significantly greater in subjects with IDDM compared to controls in all arterial segments (P≤0.001). Presence of calcification on CT was more frequently encountered in 6 of the 8 segments in subjects with IDDM, and there was statistically significantly difference for the descending aorta and abdominal aorta. CONCLUSION: Our results show that inflammatory component of atherosclerosis was more severe in all aortic segments in subjects with IDDM compared to those of controls. Presence of macroscopic calcification also detected to be more frequently encountered in the descending thoracic and abdominal aorta in subjects with IDDM. Fluorine-18-FDG PET/CT is a valuable diagnostic tool for detecting and semi-quantifying accelerated atherosclerotic inflammatory and calcific changes secondary to diabetes mellitus treated with insulin in the aortic segments and large arteries.

Atherosclerotic inflammatory activity in the aorta and its correlation with aging and gender as assessed by 18F-FDG-PET.

Recent literature demonstrates the potential of fluorine-18 fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) to detect, localize, and quantify the degree of inflammatory changes in the arterial wall due to early atherosclerosis. Our aim was to assess the correlation between the age and 18F-FDG uptake of aortic segments and determine its correlation with respect to in both age and genders. Fluorine-18-FDG uptake in aortic segments in 143 subjects (58 men, 85 women; ages 5-82 years) was evaluated in this study. Subjects were initially grouped according to the gender, and then by age (below or above 50) with at least 26 subjects per group. Mean standardized uptake value (SUV) of ascending aorta, arch, descending thoracic aorta, and abdominal aortic segments were calculated in each subject. Correlative analyses between age and mean SUV of aortic segments in all subjects were undertaken. Mean SUV between genders for all groups were also compared. There was a positive correlation between age and mean SUV of all aortic segments. The correlation values in all aortic segments were higher in subjects below 50 years old compared to those above 50 years in the entire group of patients as well as when they were subdivided and analyzed according to both genders (P<0.001). Descending thoracic and ascending aortic segments in men below 50 years of age had the highest correlation of 18F-FDG uptake and age (0.85 and 0.80, respectively) whereas abdominal aortic segments in men the above 50 years age group had the lowest correlation value (0.20). Comparison between mean SUV in four visible arterial segments between the two genders did not reveal any statistically significant difference. In conclusion, 18F-FDG uptake in aortic segments increases with age irrespective of genders. The increase with age is more significant in younger subjects compared to older subjects for both men and women. This finding may indicate a deceleration in the inflammatory component of atherosclerosis with aging in older subjects.

Oral nutritional supplements (ONSs) for cirrhotic patients undergoing liver resection assessed by ultrasound measurement of rectus femoris and anterior tibialis muscles thickness. Randomized clinical trial.

PURPOSE: We evaluated the effects of postoperative administration of (ONSs) on the liver function and the outcome of cirrhotic patients using ultrasound (US) assessment of rectus femoris (RF) and anterior tibialis (AT) muscles. PATIENTS AND METHODS: Forty-three malnourished adult hepatic patients who underwent major liver resections were recruited in this study. In the conventional diet (CD) group, the patients took water at postoperative day (POD) 0 and routine soft diet starting from POD1. In the ONS group, a commercially elemental diet was started from POD1 for 7 days postoperatively, with a target endpoint of 35-40 kcal/kg and 1.2-1.5 g/kg of protein per day. US assessment of the RF and AT muscles was done preoperatively and at POD3 and 7, including anterior-posterior (AP) diameter, lateral-lateral (LL) diameter, and cross-sectional area (CSA). Muscles' echogenicity was defined by the Heckmatt scale. The outcome of the patients was also recorded. RESULTS: Consumption of ONS preserved the measured RF and AT characteristics (AP and LL diameters and CSA) in the ONS group at POD3 and 7 compared to the CD group. Heckmatt scale was significantly increased at POD3 and 7 in the CD group compared to the ONS group. Both total protein and albumin levels at POD3 and 7 were significantly lower in the CD group compared to the ONS group [P = (0.02, 0.03) and (0.05, 0.04), respectively]. Serum phosphate was significantly lower at POD7 in the ONS group than the CD group (p = 0.04). There were significant decreases in the ICU stay and time of passing flatus (h) in the ONS group comparing with the CD group (P = 0.045 and P = 0.00, respectively). CONCLUSIONS: ONS maintains muscle mass and echogenicity of RF and AT along with better liver function and intestinal function recovery.

Portal vein thrombosis in hepatitis C virus-related cirrhotic patients: Prevalence and clinical characteristics in an Egyptian cohort.

Portal vein thrombosis is a catastrophe not uncommonly complicating hepatitis C virus-related liver cirrhosis. To estimate its prevalence and clinical characteristics, we investigated 1000 cirrhotic patients by abdominal ultrasound or Doppler study at least. Portal vein thrombosis was found in 21.6%, of whom 157 (72.7%) had malignancy. Complete portal vein thrombosis was found in 70.4%. Half of all these patients had at least one episode of portal hypertensive bleeding, a third had abdominal pain and a quarter presented with jaundice. Portal bilopathy was diagnosed in two cases (0.9%). There was significant association between severity of liver disease, ascites, male gender and site of segmental focal lesion and portal vein thrombosis.

Increased 18F-FDG uptake within the reticuloendothelial system in patients with active lung cancer on PET imaging may indicate activation of the systemic immune response.

The reticuloendothelial system (RES) cells are in the defense against certain pathogens, and in the removal of dying cells, cell debris, microorganisms, and malignant cells. Liver, spleen, and bone marrow represent the major organs with high RES activity. We hypothesized that in subjects with active lung cancer, the metabolic activity of these organs would be greater than that of the subjects with no active tumor. We have studied two groups of subjects who had undergone (18)F-FDG-PET imaging for clinical purposes. The first group consisted of 39 subjects (20 women, 19 men, mean age 64.8+/-10.2 years) with benign lung nodules as demonstrated by (18)F-FDG-PET imaging. The second group consisted of 30 subjects (18 women, 12 men; mean age 65.1+/-11 years) who were known to have active lung cancer with or without distant metastases as seen on (18)F-FDG-PET imaging. The subjects in the second group did not have any evidence of liver, spleen, bone marrow, or heart involvement on (18)F-FDG-PET images. We measured the mean SUV of the liver, spleen, bone marrow, heart, and of the contralateral unaffected lung, and compared the average SUV for these organs between the two groups. We found that the mean SUV of the liver, bone marrow, and spleen were significantly greater in subjects with evidence of active primary or metastatic lung cancer compared with those of subjects who had benign lung nodules and no evidence of active malignant disease. There was a statistically significant difference between mean SUV for organs noted above between the two groups (P<0.05). In contrast, mean SUV for the heart and contralateral normal lung did not show any significant difference between the two groups. In conclusion, the mean SUV for the major organs of RES, liver, spleen, and bone marrow were higher in subjects with active lung cancer with or without metastases than in those without active malignancy. We believe these differences in SUV may indicate a differential activation of the systemic immune response, related to the presence or absence of active lung cancer, which can be detected and quantified non-invasively through (18)F-FDG-PET imaging.

Usefulness of non attenuation corrected 18F-FDG-PET images for optimal assessment of disease activity in patients with lymphoma.

This study aimed at determining whether non attenuation corrected (NAC) positron emission tomography (PET) images, in addition to the attenuation corrected (AC) PET images, should be included in the interpretation of fluoro-18 fluorodeoxyglucose ((18)F-FDG-PET) images in patients with lymphoma. The study included 58 patients, 35 males 23 females, mean age 55+/-16 years. There were 64 superficial and 170 deep lymph node (LN) lesions. Lesion detection, uptake intensity using a three-point scale (1-mild, 2-moderate, 3- intense) and overall clarity of each lesion were compared on both PET images. Our results showed that the detection rate for superficial LN was 100% for NAC-PET and 98.4% for AC-PET images. The degree of (18)F-FDG uptake (intense, moderate and mild uptake) was 56.3%, 31.3% and 12.5% for NAC-PET images and 23.4%, 34.4% and 40.6% for AC-PET images, respectively. The overall image clarity was significantly in favor of NAC compared to AC-PET images (89% vs 20%, P<0.01). For deep LN, lesions, detection rate was for NAC and AC-PET images 95.3% and 99.4%, respectively. (18)F-FDG uptake intensity (intense, moderate and mild uptake) was 42.4%, 27.1% and 25.9% for NAC and 52.4%, 43% and 4.1% for AC-PET images, respectively. The overall image clarity for AC-PET images was superior to NAC-PET images (81.8% vs 53% P=0.01). In conclusion, NAC-PET images appeared to be superior to AC-PET images in detecting superficial LN lesions. AC-PET images are superior to NAC-PET images with regard to the deep-seated LN lesions. Therefore, AC and NAC-PET images are complimentary to each other and require to be reviewed together in the evaluation of patients with lymphoma.

Tumor metabolism measured by partial volume corrected standardized uptake value varies considerably in primary and metastatic sites in patients with lung cancer. A new observation.

Fluorine-18 fluorodeoxyglycose -position emission tomography ((18)F-FDG-PET) as an efficient staging tool for lung carcinoma; allows description and characterization of the primary tumor and of local and distant metastases in a single examination. One of the important limiting factors in quantification of metabolic parameters with PET is the partial volume effect. Our aim for this study was to delineate tumor (size) both in the primary and metastatic lesions in patients with lung cancer by using partial volume correction techniques. Thirty two patients with proven lung cancer who had (18)F-FDG-PET and computerized tomography (CT) within the last 80 days were involved in this study. They were 18 women and 14 men, with age range 43-83 years. Maximum standardized uptake values (SUVmax) in primary and metastatic lesions for all patients were measured. The lesions were categorized into 4 different Groups according to their site. Partial volume corrections were applied using the CT sizes of lesions to obtain corrected SUVmax values. Average corrected SUVmax in each lesion site was calculated and compared between the 4 Groups. A total of 81 primary and metastatic lesions were included in this analysis. They were 28 mediastinal-hilar lymph node lesions, 26 lung lesions, 11 solid organ lesions, and 16 bone marrow lesions. The average uncorrected SUVmax for the primary lung lesions, mediastinal-hilar lymph node lesions, solid organ lesions, and the bone marrow lesions before application of partial volume correction formula were 7.2+/-3.2; 7.0+/-2.7; 6.3+/-3.4 and 7.0+/-3.4, respectively. The average corrected SUVmax for the lesions in the above mentioned regions were 11+/-6, 10+/-4, 13+/-7, and 18+/-13, respectively. A statistically significant difference was observed in the average SUVmax values between lung lesions and nodal lesions compared to the bone marrow lesions. In conclusion, our findings indicate that metabolic activities of lung cancer lesions vary depending on the sites of metastatic disease.

A pilot study of changes in (18)F-FDG uptake, calcification and global metabolic activity of the aorta with aging.

Our aim was to quantify changes in the inflammatory and calcific components of atherosclerosis in the aortic wall using fluoro-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (18)F-FDGPET and contrast enhanced computerized tomography (CECT) with increasing age. Twelve subjects, 8 men and 4 women aged from 21-80 years who had both (18)F-FDG-PET and CECT of the chest and abdomen were included in this study. Subjects were grouped into three according to age. (18)F-FDG uptake in four segments of the aorta was measured. Using CECT images, aortic segmental wall volumes were measured. Wall calcification volume in each aortic segment was also measured via adaptation of a coronary artery calcium-scoring program to the aorta. Calcification volumes were then subtracted from aortic wall volumes. Each net segmental aortic wall volume was then multiplied by the accompanying mean SUV of the segment to calculate global metabolic activity (GMA) for each aortic segment. Our results showed that in each aortic wall segment, mean SUV, wall volumes, wall calcification volumes, and GMA statistically significantly increased with age. In conclusion, (18)F-FDG uptake, wall volume, wall calcification volume, and GMA in the aorta increase with aging. The (18)F-FDG uptake represents the early inflammatory component of the atherosclerotic process, whereas calcification generally represents a later and irreversible stage of the disease. Measurement and combination of PET and CECT parameters to calculate GMA may allow for optimal morphologic and functional noninvasive quantitative assessment of global aortic atherosclerotic disease.

Implications of standardized uptake value measurements of the primary lesions in proven cases of breast carcinoma with different degree of disease burden at diagnosis: does 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography predict tumor biology?

OBJECTIVES: Tumor glycolytic activity as determined by 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) imaging is an important marker of tumor biology and provides critical information about the behavior of most malignancies at different stages of the disease. This study was undertaken to determine whether the degree of FDG uptake differs between the primary breast lesions with varying disease burden at diagnosis in proven cases of breast carcinoma. MATERIALS AND METHODS: Among 250 patients enrolled for this prospective study, 174 patients with newly diagnosed breast carcinoma at different disease stages who had undergone dual time point FDG-PET before any therapeutic or surgical interventions were considered for inclusion in this analysis. These patients prospectively underwent multimodality imaging techniques, such as magnetic resonance imaging (MRI), ultrasonography, digital mammography, computed tomography (CT), and dual time point FDG-PET, as a component of a National Institutes of Health-funded project for characterizing primary breast lesions and local-regional staging. The slice with maximum FDG uptake in the region of interest (ROI) was chosen for the first time point and the second time point images for quantitative measurement of the metabolic activity of the tracer (SUVmax1 and SUVmax2, respectively). Furthermore, the percent change in SUVmax (%DeltaSUVmax) between SUVmax1 and SUVmax2 was calculated. RESULTS: The patient population (n=174) were divided into three groups for the purposes of this study. Sixty-four patients with primary and metastatic axillary lymphadenopathy (designated as group I) and 18 patients with both axillary and distant metastases (designated as group II) met the inclusion criteria for this analysis. The third group (group III) comprised of a population of 92 patients without any metastasis either at the lymph nodes or at distant sites. The mean SUVmax1, SUVmax2, and the %DeltaSUVmax in the early and delayed FDG-PET in group I (n=64) patients were as follows: primary lesion 4.8+/-3.9, 5.3+/-4.5, and 9.4+/-12.8%, respectively, and axillary lesions 3+/-2.6, 3+/-2.7, and 1.1+/-21.3%, respectively. Among the group II patients (n=18), the mean values of the primary lesion with regard to the SUVmax1, SUVmax2, and the %DeltaSUVmax were 7.7+/-6.2, 8.9+/-7.1, and 15.7+/-10.8%, respectively. The corresponding figures for the axillary lesions were 3.5+/-3.1, 3.7+/-3.1, and 6.3+/-20.9%, respectively, and those for the distant metastatic lesions were 3+/-1.4, 3.1+/-1.2, and 8.5+/-21.2%, respectively. The mean SUVmax1, SUVmax2, and the %DeltaSUVmax of the primary lesion of group III patients (n=92) without any metastasis were 2.9+/-2.7, 3.4+/-2.4, and 4.5+/-4.2%, respectively. Unifactorial ANOVA of the three parameters among the primary lesions of these three groups were statistically significant with regard to the mean SUVmax1 (p=0.01) and SUVmax2 (p=0.01). These values in the primary lesions were highest in group II (those with both axillary and distant metastases), followed by group I (those with only metastatic axillary adenopathy) and group III (patients without any metastasis), and could be related to the more aggressive tumor biology in group II. CONCLUSION: The findings provide evidence that among the lesions with varying disease burden at diagnosis, the FDG uptake is highest in cases with both axillary and distant metastasis, followed by those with axillary metastasis and then by those with no metastatic disease. These provide in vivo insight into tumor biology as FDG uptake is regarded as a surrogate marker of the same.

Significance of incidental fluorodeoxyglucose uptake in the parotid glands and its impact on patient management.

BACKGROUND AND OBJECTIVES: Minimal-to-low grade fluorodeoxyglucose (FDG) uptake in the parotid glands is regarded as a normal variant in a whole-body survey with FDG-PET. Not frequently, however, a relatively intense or asymmetric FDG uptake is encountered in the parotid glands. The aim of this study was to determine the causes and characteristics of this 'FDG accumulation of uncertain significance' in the parotid glands in patients without any known or suspected pathologies at the time of whole-body FDG-PET. In addition, we also examined patients in whom there was no documented evidence of parotid pathology before FDG-PET scan and a suspicion of disease involvement was first raised in the reports in view of focal uptake in the FDG-PET images. MATERIALS AND METHODS: A total of 25 patients with 49 PET examinations [46 PET and three PET/computed tomography (CT) scans] were identified from the retrospective examination of PET reports and were analyzed in this study. Only those cases with no earlier history of disease involvement of parotid gland or known parotid pathology before FDG-PET were selected for this analysis. These patients were selected from a population of patients with a known malignancy elsewhere who underwent conventional whole-body FDG-PET or PET/CT for staging, disease viability assessment, or treatment monitoring purposes and had demonstrated varying patterns of FDG uptake (unilateral, bilateral, symmetric, or asymmetric) in the parotid glands. FDG uptake in the parotid glands was reported to be of uncertain significance in the majority of these patients and further correlation was suggested in the PET reports. In five patients with asymmetric and focally enhanced FDG uptake, a suspicion of disease involvement was raised in the reports. The results of appropriate correlative investigations with MRI, low-dose nonenhanced attenuation CT images (based on PET/CT scans), and histopathology (in cases in which focal lesions were revealed by the anatomic imaging modalities and biopsy was performed) carried out subsequent to the FDG-PET scans were reviewed for a definitive conclusion with regard to the significance of the FDG uptake in the parotid glands in these patients. In the absence of any focal pathology, clinical and follow-up FDG-PET data were reviewed for a logical conclusion, which were available in a majority of these patients. Standardized uptake values (maximum) were calculated by generating a manual region of interest over FDG activity. The pattern and the intensity of the FDG uptake were correlated with the final diagnosis. RESULTS: In six of the 25 patients with diffuse and symmetrical FDG uptake no clearcut pathology was demonstrated by clinical or radiological examinations. Five patients of this subgroup also demonstrated associated enhanced FDG activity in the submandibular salivary glands. Nineteen patients (76%) demonstrated asymmetric FDG uptake. Among these, focally enhanced uptake was observed in seven patients (28% of the total number of patients and 36.8% of the patients who demonstrated asymmetric FDG uptake in the parotids). Twelve patients (48% of total patients and 63.2% of the patients who demonstrated asymmetric FDG uptake) demonstrated asymmetric and diffuse FDG uptake pattern. No revelation of disease either by the MRI or follow-up clinical and FDG-PET examinations was observed in patients with asymmetric diffuse uptake. Five of the seven patients, who had asymmetric focal uptake in one of the parotids, were found to have focal lesions in either correlative MRI or low-dose nonenhanced CT. The final diagnosis based upon histopathology revealed primary parotid tumors (e.g., Warthin's tumor and pleomorphic adenoma, which presented as FDG-avid parotid incidentaloma) or metastatic disease involvement. CONCLUSION: Both the pattern and intensity of FDG uptake have important implications for differential diagnosis in the salivary glands in whole-body FDG-PET. A bilaterally symmetrical increased uptake is usually physiological. An asymmetrical uptake, especially when focal, would warrant further radiological and histopathological correlation to rule out disease involvement. At times, this can lead to the detection of an asymptomatic hitherto unknown etiology, which would have been otherwise interpreted as a metastatic disease in the background of an existing malignancy in these patients; this is noteworthy as it may have a bearing on the subsequent management of these patients.

Structural and functional imaging correlates for age-related changes in the brain.

In recent years, investigators have made significant progress in documenting brain structure and function as it relates to aging by using positron emission tomography, conventional magnetic resonance (MR) imaging, advanced MR techniques, and functional MR imaging. This review summarizes the latest advances in understanding physiologic maturation and aging as detected by these neuroimaging modalities. We also present our experience with MR volumetric and positron emission tomography analysis in separate cohorts of healthy subjects in the pediatric and adult age groups respectively. Our results are consistent with previous studies and include the following: total brain volume was found to increase with age (up to 20 years of age). Whole brain metabolism and frontal lobe metabolism both decrease significantly with age (38% and 42%, respectively), whereas cerebellar metabolism does not show a significant decline with age. Defining normal alterations in brain function and structure allows early detection of disorders such as Alzheimer's and Parkinson's diseases, which are commonly associated with normal aging.

Determination of age-related changes in structure and function of skin, adipose tissue, and skeletal muscle with computed tomography, magnetic resonance imaging, and positron emission tomography.

In this article, we report quantitative preliminary data obtained from retrospective analysis of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and combined PET-computed tomography (PET/CT) examinations in subjects ages 3 to 84 years pertaining to changes in the metabolism of skin, subcutaneous adipose tissue, visceral adipose tissue, and skeletal muscle with age, as well as age-related changes in skeletal muscle attenuation. We also propose a new method for identifying hypermetabolic brown fat on FDG-PET. Finally, we present a review of the literature regarding reported age-related structural and functional changes that occur in skin, fat, and skeletal muscle. Using FDG-PET, We evaluated 213 subjects for changes in the metabolism of skin, adipose tissue, and skeletal muscle with aging. Thirty-two separate subjects were chosen to measure maximum standardized uptake value (SUV) of hypermetabolic brown fat on dual-time point PET imaging. Finally, 15 subjects evaluated by PET/CT were selected to measure changes in metabolism and attenuation of skeletal muscle, and changes in metabolism of adipose tissue with aging. We found that skin, fat, and skeletal muscle all demonstrate significant (P < 0.05) increases in SUV with increasing age on PET imaging. Dual-time point PET imaging demonstrates increasing FDG uptake of hypermetabolic brown fat in various regions studied. Finally, our PET/CT studies revealed statistically insignificant (P > 0.05) decreases in SUV of adipose tissue with aging and the opposite trend in skeletal muscles (P > 0.05). Skeletal muscle attenuation in the various regions studied was found to significantly decrease with age (P < 0.05). Our study shows notable trends in metabolism and attenuation of skeletal muscle and metabolism of skin and adipose tissue that occur with normal aging. We hope that the methodologies and data we present here will serve as a useful starting point for those interested in conducting future prospective research on age-related changes in these structures.

Novel quantitative techniques for assessing regional and global function and structure based on modern imaging modalities: implications for normal variation, aging and diseased states.

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.

Assessment of age-related morphological and functional changes of selected structures of the head and neck by computed tomography, magnetic resonance imaging, and positron emission tomography.

The head and neck is a complex anatomical region that can be evaluated using many imaging modalities. It is important to discern normal structures from ones that are affected by disease and to study how these structures change in their morphological and functional properties with aging. Therefore, using magnetic resonance imaging (MRI), we retrospectively evaluated volumes of the parotid glands, submandibular glands, thyroid gland, tongue, soft palate, and lingual tonsils in 64 subjects ages 13 to 81 years. Volume, attenuation (HU), and metabolic activity (maximum SUV) of the parotid, submandibular, and thyroid glands were assessed retrospectively using positron emission tomography/computed tomography (PET/CT) imaging in 35 subjects ages 10 to 76 years. Metabolic activity (maximum SUV) of the parotid, submandibular, and sublingual glands; tongue; adenoids; and tonsils (lingual and palatine) were evaluated retrospectively using PET imaging in 15 subjects ages 6 to 20 years. Metabolic volumetric products of the parotid, submandibular, and thyroid gland were calculated and analyzed with increasing age in subjects who underwent PET/CT imaging. Structures that exhibited statistically significant changes (P < 0.05) with increasing age included the submandibular glands, thyroid gland, soft palate, and adenoids. The CT volume of the submandibular glands increased with age, and the attenuation decreased with age with statistical significance. The thyroid gland volume, as measured using MRI, showed a statistically significant decrease with aging. The volume of the soft palate and lingual tonsils, as measured by MRI, exhibited a statistically significant decrease in volume with aging. The maximum SUV of the adenoids demonstrated a statistically significant decrease with aging. In conclusion, CT, MRI, and PET may be used to quantitatively and qualitatively assess structures of the head and neck and are useful in the assessment of structural and functional changes of these structures with aging.

Detection of age-related changes in thoracic structure and function by computed tomography, magnetic resonance imaging, and positron emission tomography.

It is useful to understand the normal changes in structure and function in the thorax that occur with age. Thus, we present the following quantitative preliminary data obtained from retrospective quantitative analysis of computed tomography (CT) and positron emission tomography (PET) examinations in subjects 0 to 90 years of age: Mean lung standard uptake values were found to significantly increase with increasing age and with increasing body mass index (BMI). Mean lung attenuation was seen to statistically significantly decrease with increasing age in subjects who had a CT scan, had a nonsignificant tendency to decrease with increasing age in subjects with a PET/CT scan, had a nonsignificant tendency to increase with increasing BMI, and was seen to significantly increase with increasing mean lung standard uptake values. Mean lung volumes were not noted to significantly change with increasing age in adult subjects whether or not they were normalized to the craniocaudal thoracic lengths, although mean lung volumes significantly increased with increasing age in pediatric subjects. Mean lung volumes had a nonsignificant tendency to decrease with increasing BMI, although normalized mean lung volumes significantly decreased with increasing BMI. Lung metabolic volumetric products were not noted to significantly change with increasing BMI or with increasing age. In this work, we also review the literature regarding normal structural and functional changes in the thorax with age.

The aging of the heart and blood vessels: a consideration of anatomy and physiology in the era of computed tomography, magnetic resonance imaging, and positron emission tomographic imaging methods with special consideration of atherogenesis.

Physicians have long told their patients that the doctor's job is to help patients "get as old as they can." As physicians, we have been aided in this objective by many other scientists in other disciplines. The entity of aging and its related changes blends imperceptibly with a variety of age-related diseases. However, these entities do appear to be separate though interrelated. Curing disease is important and a goal that we all work toward to add years to life expectancy. Here, we consider aging as it affects the heart and great vessels and as it serves to influence and support, if not cause, age-related cardiac diseases. This relationship is drawn as cardiac mechanics, hemodynamics, perfusion, metabolism and innervation, anatomy, and pathophysiology are each considered. The effects of aging are presented in 2 sections related to the early and recent "spikes" in aging related information. The latter is largely based in recent developments in chemistry, genetic engineering, molecular biology and the new imaging methods. The purpose of this manuscript is to present these new imaging methods, especially PET, and their impact on the second "spike." This is emphasized particularly in the second half of this review. As a method of demonstrating these imaging tools and their finest potential application, we decided to "showcase" atherosclerosis as the age-related disease for which these methods have made their greatest impact, for which yet more is promised, and for which the influence on longevity is most obvious. The application of positron emission tomography and other imaging methods to the characterization and image identification of atherosclerotic plaques and particularly the "vulnerable" plaque is emphasized. Yet, even with the eradication of coronary disease, the potential for very long life would not be likely. Only with the identification and eradication of the causative factors of aging can this possibility have a chance of becoming reality.

Age-related structural and functional changes in the breast: multimodality correlation with digital mammography, computed tomography, magnetic resonance imaging, and positron emission tomography.

Preliminary results generated from digital mammography, computed tomography, magnetic resonance imaging, and (18)F-fluorodeoxyglucose positron emission tomography demonstrate concordant findings of decreasing glandular tissue and decreasing metabolic activity with increasing age. These results are presented in the context of a detailed literature review summarizing age-related changes in the breast, both from the histologic/physiologic and the imaging perspectives. We also discuss potential applications of this approach and emphasize the importance of new advanced imaging technologies to offer high levels of quantitative precision for tissue characterization for research and clinical purposes.

Assessment of age-related changes in abdominal organ structure and function with computed tomography and positron emission tomography.

With the size of the aged population in the United States expected to grow considerably during the next several decades, the number of imaging studies performed on such aged individuals will similarly increase. Thus, it is important to understand normal age-related changes in the structural and functional imaging appearance of the abdominal organs. We therefore present preliminary data and a review of the literature relevant to structural and functional changes in the abdominal organs of children and older adults. In a retrospective study of both adult and pediatric populations, we used computed tomography (CT), positron emission tomography (PET), and PET/CT imaging to investigate age-associated changes in size, attenuation, and metabolic function of the abdominal organs. Organs of interest include the liver, spleen, pancreas, kidneys, adrenal glands, stomach, small bowel, colon, and rectum. Although volumes of adult liver, spleen, pancreas, and kidneys do not change significantly with age, adult left and right adrenal gland volumes do significantly increase with age (r = 0.2823, P = 0.0334, and r = 0.3676, P = 0.0049, respectively). Also, the attenuation of adult liver (r = -0.2122, P = 0.0412), spleen (r = -0.4508, P < 0.0001), pancreas (r = -0.5124, P = 0.0007), and left and right adrenal gland (r = -0.5835, P < 0.0001 and r = -0.6135, P < 0.0001, respectively) decrease significantly with increasing age. Every organ studied in the pediatric population demonstrates a positive association between organ volume and age. Significant age-related changes in organ function are noted in the adult liver and small bowel, with the liver demonstrating a positive association between metabolic activity and age (r = 0.4434, P = 0.0029) and the small bowel showing an inverse association between mean small bowel standardize uptake value and age (r = -0.2435, P = 0.0174). Also, the maximum overall small bowel and colon metabolic activity in children increases with age (r = 0.6478, P = 0.0008). None of the other organs studied (ie, spleen, pancreas, adrenal glands, stomach, colon, rectum) demonstrate significant changes in metabolism with advancing age. The metabolic volumetric product (calculated as the product of organ volume and mean organ SUV) of the liver and spleen does not change significantly with age. In conclusion, various abdominal organs demonstrate differential changes in volume, attenuation, and/or metabolism with increasing age in pediatric and adult populations.