The precision of positron emission tomography: theory and measurement

The limits of quantitation with positron emission tomography (PET) are examined with respect to the noise propagation resulting from radioactive decay and other sources of random error. Theoretical methods for evaluating the statistical error have been devised but seldom applied to experimental data obtained on human subjects. This paper extends the analysis in several ways: (1) A Monte Carlo method is described for tracking the propagation of statistical error through the analysis of in vivo measurements; (2) Experimental data, obtained in phantoms, validating the Monte Carlo method and other methods are presented; (3) A difference in activation paradigm, performed on regional CBF (rCBF) data from five human subjects, was analyzed on 1.6-cm diameter regions of interest to determine the mean fractional statistical error in PET tissue concentration and in rCBF before and after stereotactic transformation; and (4) A linear statistical model and calculations of the various statistical errors were used to estimate the magnitude of the subject-specific fluctuations under various conditions. In this specific example, the root mean squared (RMS) noise in flow measurements was about three times higher than the RMS noise in the concentration measurements. In addition, the total random error was almost equally partitioned between statistical error and random fluctuations due to all other sources.     

Left ventricular diastolic dysfunction as assessed by echocardiography in metabolic syndrome.

The purpose of the present study was to elucidate the cardiac structure and function in patients who have metabolic syndrome but no history of cardiovascular disease by analyzing echocardiographic findings. Echocardiographic examination was performed to screen for cardiovascular disease in 135 patients who were in their sixties. Patients were divided into metabolic syndrome (n=65, age: 65+/-2.7 years) and non-metabolic syndrome (n=70, age: 66+/-2.5 years) groups based on the criteria for metabolic syndrome proposed by the Japanese Society of Hypertension and seven other societies in 2005. The left ventricular (LV) wall thickness and dimension were measured by M-mode echocardiography. The relative wall thickness, LV mass index, and LV ejection fraction (LVEF) were calculated. LV diastolic function was assessed by the peak velocity of early rapid filling (E velocity) and the peak velocity of atrial filling (A velocity), and the ratio of E to A (E/A) was assessed by the transmitral flow. The Tei index, which reflects both LV diastolic and systolic function, was also calculated. There were no differences in relative wall thickness, LV mass index, or LVEF between the two groups. However, both the EIA and Tei index were significantly different between the metabolic syndrome (0.66+/-0.14 and 0.36+/-0.07, respectively) and non-metabolic syndrome (0.88+/-0.25 and 0.29+/-0.09) groups (p<0.001). These results indicate that patients with metabolic syndrome can have cardiac diastolic dysfunction even if they have neither LV hypertrophy nor systolic dysfunction.     

A human friendly reporting and database system for brain PET analysis

We have developed a human friendly reporting and database system for clinical brain PET (Positron Emission Tomography) scans, which enables statistical data analysis on qualitative information obtained from image interpretation. Our system consists of a Brain PET Data (Input) Tool and Report Writing Tool. In the Brain PET Data Tool, findings and interpretations are input by selecting menu icons in a window panel instead of writing a free text. This method of input enables on-line data entry into and update of the database by means of pre-defined consistent words, which facilitates statistical data analysis. The Report Writing Tool generates a one page report of natural English sentences semi-automatically by using the above input information and the patient information obtained from our PET center’s main database. It also has a keyword selection function from the report text so that we can save a set of keywords on the database for further analysis. By means of this system, we can store the data related to patient information and visual interpretation of the PET examination while writing clinical reports in daily work. The database files in our system can be accessed by means of commercially available databases. We have used the 4th Dimension database that runs on a Macintosh computer and analyzed 95 cases of^I8F-FDG brain PET studies. The results showed high specificity of parietal hypometabolism for Alzheimer’s patients.     

Arpp,a new homolog of carp,is preferentially expressed in type 1 skeletal muscle fibers and is markedly induced by denervation

In this study, we isolated and characterized a murine counterpart of the human Arpp (hArpp) gene. Sequence analysis revealed that the murine Arpp (mArpp) gene is almost identical to the Ankrd2 gene, which has recently been isolated as a mouse gene induced in stretched skeletal muscle. The mArpp gene encodes a protein of 332 amino acids that contains four well-conserved ankyrin-repeat domains in the central portion of the protein. The amino acid sequence of mArpp protein (mArpp) is highly homologous to that of mouse cardiac-restricted ankyrin-repeat protein (Carp), which is proposed to be a putative genetic marker for cardiac hypertrophy. Immunohistochemical analysis revealed that mArpp is preferentially expressed in type 1 skeletal muscle fibers, and that mArpp is localized in both the nucleus and the sarcomeric I-band of muscle fibers, suggesting that Arpp may function as a nuclear and sarcomeric protein. Furthermore, mArpp was also expressed in neurons of the cerebellum and cerebrum, the islets of Langerhans in the pancreas, and the esophageal epithelium, suggesting that mArpp may play a functional physiologic role in brain, pancreas, and esophagus as well as in type 1 muscle fibers. Interestingly, although mArpp was localized in both nucleus and cytoplasm in neurons, its localization was restricted to nucleus in pancreas and esophagus, suggesting that intracellular localization of mArpp is regulated in a tissue-specific manner. Furthermore, we found that mArpp- and Carp-expression in skeletal muscle were markedly up-regulated after denervation. Although the elevated expression level of Carp was kept only for two weeks after denervation, that of Arpp was kept at least for 4 weeks, suggesting that mArpp and Carp may play distinct functional roles in denervated skeletal muscle.     

Quantitative evaluation of regional pulmonary ventilation using PET and nitrogen-13 gas

A new quantitative method, "Simultaneous Exponential Equation method" (SEE), has been developed for the analysis of pulmonary ventilation studies using 13N-labeled nitrogen gas and positron emission computed tomography. This method uses Kety's model assuming insolubility of nitrogen gas in blood or tissues. Activity in poorly ventilated regions does not reach the equilibrium in the so-called equilibrium scan (EQ) performed following 3 or 4 min of washin. Therefore EQ images do not represent lung volume images nor do they provide the initial value of washout phase. Our method corrects for these transient phenomena observed during EQ scan and yields idealistic equilibrium state images (lung volume images) as well as more accurate regional ventilatory time constants than a modified Stewart-Hamilton (A/H) method and tomograms of high resolution.     

Ingestion of High β-Glucan Barley Flour Enhances the Intestinal Immune System of Diet-Induced Obese Mice by Prebiotic Effects

The prebiotic effect of high β-glucan barley (HGB) flour on the innate immune system of high-fat model mice was investigated. C57BL/6J male mice were fed a high-fat diet supplemented with HGB flour for 90 days. Secretory immunoglobulin A (sIgA) in the cecum and serum were analyzed by enzyme-linked immunosorbent assays (ELISA). Real-time PCR was used to determine mRNA expression levels of pro- and anti-inflammatory cytokines such as interleukin (IL)-10 and IL-6 in the ileum as well as the composition of the microbiota in the cecum. Concentrations of short-chain fatty acids (SCFAs) and organic acids were analyzed by GC/MS. Concentrations of sIgA in the cecum and serum were increased in the HGB group compared to the control. Gene expression levels of IL-10 and polymeric immunoglobulin receptor (pIgR) significantly increased in the HGB group. HGB intake increased the bacterial count of microbiota, such as Bifidobacterium and Lactobacillus. Concentrations of propionate and lactate in the cecum were increased in the HGB group, and a positive correlation was found between these organic acids and the IL-10 expression level. Our findings showed that HGB flour enhanced immune function such as IgA secretion and IL-10 expression, even when the immune system was deteriorated by a high-fat diet. Moreover, we found that HGB flour modulated the gut microbiota, which increased the concentration of SCFAs, thereby stimulating the immune system.     

Vascular reserve in chronic cerebral ischemia measured by the acetazolamide challenge test: comparison with positron emission tomography.

PURPOSETo determine the value of the acetazolamide challenge test with stable xenon-enhanced CT (Xe CT) for making therapeutic decisions in patients with chronic cerebrovascular disease.METHODSWe compared the Xe CT-measured acetazolamide response with various measures obtained by positron emission tomography. We performed both a positron emission tomographic scan and a Xe CT study in 11 patients with chronic cerebral ischemic diseases within a 1-week interval. An increase of cerebral blood flow after injection of acetazolamide was expressed as delta AT. Regional cerebral blood flow, cerebral oxygen metabolism, oxygen extraction fraction, and cerebral blood volume were measured with oxygen-15-labeled gases by positron emission tomography.RESULTSIn low-cerebral blood flow regions, decreased delta AT was accompanied by a significant elevation of oxygen extraction fraction and cerebral blood volume, compared with oxygen extraction fraction and cerebral blood volume in regions of normal delta AT. Plotting of regional data indicated that delta was significantly dependent on oxygen extraction fraction and cerebral blood volume. The area of decreased vascular reserve determined by the Xe CT image corresponded to the area of "misery perfusion" determined by positron emission tomography.CONCLUSIONThe acetazolamide challenge test with Xe CT may offer an alternative to positron-emission tomography in detecting lesions with elevated oxygen extraction fraction and cerebral blood volume (misery perfusion) that result from chronic hemodynamic stress.     

Gas-tissue autoradiography using [15O] molecular oxygen for visualization of mitochondrial oxygen fixation in brain slices

We have developed a novel in vitro autoradiographic method of visualizing oxygen fixation using [15O]O(2). Brain slices (400 microm) are preincubated in Krebs-Ringer phosphate buffer and exposed to [15O]O(2) with carrier O(2) for 10 min on slide glass or on a Millicell-CM membrane in a chamber. After the 15O(2) exposure, the brain slices are placed in contact with an imaging plate. The autoradiograms are analyzed with MacBas to obtain images of the distribution of radioactivity. The [15O]O(2) fixation was more extensive in the gray matter (striatum, thalamus and cerebral cortex) than in the white matter. The fixation of [15O]O(2) in brain slices decreased dose dependently with NaCN concentration. These results indicate that [15O]O(2) is converted into [15O]H(2)O in the brain tissue according to the activity of mitochondrial electron transfer and remains in the tissue. This method provides information regarding the basic oxygen consumption of brain slices of rat and mouse under conditions of sufficient O(2) delivery, which reflects mitochondrial electron transport.     

Further isolation and characterization of grammistins from the skin secretion of the soapfish Grammistes sexlineatus.

Soapfishes contain peptide toxins (grammistins) in the skin secretion. Two grammistins (Gs 1 and Gs 2) and six grammistins (Pp 1, Pp 2a, Pp 2b, Pp 3, Pp 4a and Pp 4b) have already been isolated from Grammistes sexlineatus and Pogonoperca punctata, respectively. In this study, five grammistins (Gs A-E), together with grammistins Gs 1 and Gs 2, were further isolated from G. sexlineatus by gel filtration and reverse-phase HPLC. Sequence analyses revealed that grammistins Gs A (28 residues) and Gs C (26 residues) are analogous to grammistin Pp 3 and grammistin Gs B (12 residues) to grammistin Pp 1, while grammistins Gs D (13 residues) and Gs E (13 residues) are identical with grammistins Pp 1 and Pp 2b, respectively. Grammistins Gs A-C exhibited antibacterial activity with a broad spectrum against nine species of bacteria in common with the other grammistins but had no hemolytic activity differing from the other grammistins. Grammistins Gs A-E, Gs 1 and Gs 2 could release carboxyfluorescein entrapped within liposomes made of either phosphatidylcholine or phosphatidylglycerol/phosphatidylcholine (3:1), demonstrating their membrane-lytic activity. However, no clear relationship between the membrane-lytic activity and the biological activity of grammistins was recognized.