Abstract Background Brain imaging studies of early Alzheimer's disease (AD) have shown decreased metabolism predominantly in the posterior cingulate cortex (PCC), medial temporal lobe, and inferior ...parietal lobe. This study investigated functional connectivity between these regions, as well as connectivity between these regions and the whole brain. Methods Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies were performed in subjects with early AD, mild cognitive impairment (MCI), and normal controls. Results The data indicate both decreased fiber connections and disrupted connectivity between the hippocampus and PCC in early AD. The MCI group showed reduced fiber numbers derived from PCC and hippocampus to the whole brain. Conclusions The fMRI and DTI results confirmed decreased connectivity from both the PCC and hippocampus to the whole brain in MCI and AD and reduction in connectivity between these two regions, which plausibly represents an early imaging biomarker for AD.
The introduction of fast scintillators with good stopping power for 511-keV photons has renewed interest in time-of-flight (TOF) PET. The ability to measure the difference between the arrival times ...of a pair of photons originating from positron annihilation improves the image signal-to-noise ratio (SNR). The level of improvement depends upon the extent and distribution of the positron activity and the time resolution of the PET scanner. While specific estimates can be made for phantom imaging, the impact of TOF PET is more difficult to quantify in clinical situations. The results presented here quantify the benefit of TOF in a challenging phantom experiment and then assess both qualitatively and quantitatively the impact of incorporating TOF information into the reconstruction of clinical studies. A clear correlation between patient body mass index and gain in SNR was observed in this study involving 100 oncology patient studies, with a gain due to TOF ranging from 1.1 to 1.8, which is consistent with the 590-ps time resolution of the TOF PET scanner. The visual comparison of TOF and non-TOF images performed by two nuclear medicine physicians confirmed the advantages of incorporating TOF into the reconstruction, advantages that include better definition of small lesions and image details, improved uniformity, and noise reduction.
We assessed the prevalence, awareness, treatment and control of hypertension in patients with moderate chronic kidney disease (CKD) under nephrological care in Germany. In the German Chronic Kidney ...Disease (GCKD) study, 5217 patients under nephrology specialist care were enrolled from 2010 to 2012 in a prospective observational cohort study. Inclusion criteria were an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2 or overt proteinuria in the presence of an eGFR>60 mL/min/1.73 m2. Office blood pressure was measured by trained study personnel in a standardized way and hypertension awareness and medication were assessed during standardized interviews. Blood pressure was considered as controlled if systolic < 140 and diastolic < 90 mmHg. In 5183 patients in whom measurements were available, mean blood pressure was 139.5 ± 20.4 / 79.3 ± 11.8 mmHg; 4985 (96.2%) of the patients were hypertensive. Awareness and treatment rates were > 90%. However, only 2456 (49.3%) of the hypertensive patients had controlled blood pressure. About half (51.0%) of the patients with uncontrolled blood pressure met criteria for resistant hypertension. Factors associated with better odds for controlled blood pressure in multivariate analyses included younger age, female sex, higher income, low or absent proteinuria, and use of certain classes of antihypertensive medication. We conclude that blood pressure control of CKD patients remains challenging even in the setting of nephrology specialist care, despite high rates of awareness and medication use.
Purpose To investigate the role of 18-fluorine-fluorodeoxyglucose positron emission tomography/computerized tomography (18 F-FDG PET/CT) in the preoperative prediction of the presence and extent of ...neck disease in patients with oral/head and neck cancer. Patients and Methods Seventy patients were enrolled in the study, 47 of whom had a clinically negative neck (N0), 19 of whom had a clinically positive unilateral neck (N+), and 4 of whom were negative on 1 side of the neck and positive on the other. Each patient underwent a PET/CT study before undergoing selective neck dissection for N0 disease or modified radical neck dissection for N+ disease. Tissues were submitted for histopathologic examination and were oriented for the pathologist as to the oncologic levels so as to permit correlation between histopathologic findings and the imaging results. Results The sensitivity and specificity of the PET/CT procedure were 79% and 82% for the N0 neck, and 95% and 25% for the N+ neck. One hundred ninety-two (11.4%) of the 1,678 nodes identified at histopathology were positive for metastases. The overall nodal sensitivity and specificity were 48% and 99%, respectively. Conclusion In patients with clinically negative necks, a negative test would not help the surgeon in the management strategy of the patient because of the rate of false-negative results, but a positive test can diagnose metastatic deposits with a high positive predictive value. In patients with clinically positive necks, a positive test will confirm the presence of disease, although false-negative lymph nodes were additionally identified in these clinically positive necks. With respect to nodes, the sensitivity of the imaging procedure is such that the results could not help the surgeon in deciding which level to dissect and which to spare. In the final analysis, the head and neck oncologic surgeon should not depend on the results of the PET/CT scan to determine which patients will benefit from neck dissection. Rather, time-honored principles of neck surgery should be followed, particularly with regard to the liberal execution of prophylactic neck dissections in patients with clinically N0 necks.
The study of educational production functions, the relationship between educational funding and student outcomes has been ever-evolving with contradictory assertions. National research by leaders in ...the field, such as Hanushek (1994, 1996), has found no relationship, while others examining the same evidence, such as Hedges, Laine, and Greenwald (1994a), have seen significant evidence the contrary. Both sides have agreed that national examinations are too broad, and the focus of research must be more localized to find accurate and exact results.New Hampshire has been at the center of an educational funding dispute for more than 40 years (Lockwood, 1995). The inequity between school districts in New Hampshire while retaining similar demographics made it an ideal candidate for an educational production function study. This study used a hierarchical multiple regression study to examine what types of funding had the most significant impact on student outcomes. The study examined a cohort of over 16,000 students in 116 district data points over six and ten years of expenditures to have as robust a subject of study as possible. The study used free and reduced lunch percentages and special education as control variables to gain an accurate view of the impact of the independent variables. The three independent variables, which accounted for a complete examination of total expenditures, consisted of regular instruction, combined support expenditures, and all remaining expenditures not included in previous categories. These variables were then measured at the six-year average in the hierarchical multiple regression for statistical significance compared to a six-year average of standardized mathematics and reading scores and at the ten-year average against graduation rates.After norming through beta coefficients, the results showed that the district saw roughly a one percent increase in all three independent variables for every thousand dollars that districts spent above the mean for regular instruction expenditures. The study also revealed that for every thousand dollars districts spent in addition to the mean on combined support expenditures, districts saw roughly a one percent increase in reading scores, a one-half percent increase in mathematics scores, and nearly a two percent increase in graduation rate was indicated. Additionally, the study showed that districts that had expenditures of 1,000 dollars above the mean focused on all other expenditures had reading scores that were reduced by 1.89 percent, mathematics scores that were reduced by 1.34 percent, and a .65 percent reduction in the graduation rate. All independent variables of the study were shown to have statistical significance (p < .0005) to the three dependent variables.Further study is necessary to break down the combined support expenditure and all other expenditure categories to ascertain which individual categorical expenditures had the most significant influence on student outcomes. Examining the role of teacher experience and education levels on student outcomes in the regular instruction expenditure category are also warranted. Additional study is also recommended within New Hampshire of other cohorts to replicate this study’s results among different student groupings. As educational funding remains a complex and controversial issue in New Hampshire, any additional knowledge of adequate funding levels and prioritization may help alleviate some of the funding issues in New Hampshire districts.
Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Previous genome-wide association studies (GWAS) of 300 000 genotyped variants identified MN-associated loci at HLA-DQA1 ...and PLA2R1.
We used a combined approach of genotype imputation, GWAS, human leucocyte antigen (HLA) imputation and extension to other aetiologies of chronic kidney disease (CKD) to investigate genetic MN risk variants more comprehensively. GWAS using 9 million high-quality imputed genotypes and classical HLA alleles were conducted for 323 MN European-ancestry cases and 345 controls. Additionally, 4960 patients with different CKD aetiologies in the German Chronic Kidney Disease (GCKD) study were genotyped for risk variants at HLA-DQA1 and PLA2R1.
In GWAS, lead variants in known loci rs9272729, HLA-DQA1, odds ratio (OR) = 7.3 per risk allele, P = 5.9 × 10
and rs17830558, PLA2R1, OR = 2.2, P = 1.9 × 10
were significantly associated with MN. No novel signals emerged in GWAS of X-chromosomal variants or in sex-specific analyses. Classical HLA alleles (DRB1*0301-DQA1*0501-DQB1*0201 haplotype) were associated with MN but provided little additional information beyond rs9272729. Associations were replicated in 137 GCKD patients with MN (HLA-DQA1: P = 6.4 × 10
; PLA2R1: P = 5.0 × 10
). MN risk increased steeply for patients with high-risk genotype combinations (OR > 79). While genetic variation in PLA2R1 exclusively associated with MN across 19 CKD aetiologies, the HLA-DQA1 risk allele was also associated with lupus nephritis (P = 2.8 × 10
), type 1 diabetic nephropathy (P = 6.9 × 10
) and focal segmental glomerulosclerosis (P = 5.1 × 10
), but not with immunoglobulin A nephropathy.
PLA2R1 and HLA-DQA1 are the predominant risk loci for MN detected by GWAS. While HLA-DQA1 risk variants show an association with other CKD aetiologies, PLA2R1 variants are specific to MN.
Known errors in the standardized uptake value (SUV) caused by variations in subject weights W encountered can be corrected by lean body mass or body surface area (bsa) algorithms replacing W in ...calculations. However this is infrequently done. The aims of the work here are: quantify sensitivity to W, encourage SUV correction with an approach minimally differing from tradition, and show what improvements in the SUV coefficient of variation (cv) for a population can be expected.
Selected for analyses were 2-deoxy-2-F-18fluoro-D-glucose (FDG) SUV data from positron emission tomography (PET) and PET/computed tomography (CT) scans at the University of Tennessee as well as from the literature. A weight sensitivity index was defined as -n=slope of ln(SUV/W) vs. lnW. The portion of the SUV variability due to this trend is removed by using the defined formula: see text, or a virtually equal SUVm using formula: see text, with Q and ID being tissue specific-activity and injected dose. formula: see text measures performance. Adapting to animal studies' tradition, formula: see text is preferred over the conventional formula: see text.
For FDG in adults formula: see text from averaging over most tissues. In children, however, formula: see text. Tissues have the same index if their influx constants are independent of W. Suggested, therefore, is a very simplified formula: see text, which is dimensionless and keeps the same population averages as traditional SUVs. It achieves formula: see text. Hence, for cv's of SUVs below approximately 1/3 improvements over tradition are possible, leading to F's<0.95. Accounting additionally for height, as in SUVbsa, gives very little improvement over the simplified approach here and gives essentially the same F's as SUVm.
Introduced here is a weight index useful in reducing variability and further understanding the SUV. Addressing weight sensitivity is appropriate where the cv of the SUVs is below about 1/3. Proposed is the very simple approach of using an average of an adult patient's weight and approximately 70 kg for FDG SUV calculations. Unlike other approaches the dimensionless population average of SUVms is unchanged from tradition.
The positron emission tomography (PET) clinical utility of the sensitivity (gamma) of uptake (Q) to a change in plasma glucose concentration (C) is investigated.
Gamma is obtained from data as ln(Q ...(2)/Q (1)) / ln(C(2)/C(1)), using previously published intrapatient studies varying C within a single patient and some interpatient ones. It can be theoretically related to the half-saturation constant in the Michaelis-Menten quantification of competitive uptake. One of its uses is making uptake corrections for desired vs. actual C using Q(2) = Q(1) (C(2)/C(1))(gamma).
Intrapatient studies proved to be preferable to interpatient ones, and a 2-deoxy-2-F-18fluoro-D-glucose (FDG)-PET survey with analyses for gamma yielded the following result: usually the gamma values of tumors and brain tissues were near -1, whereas those of other noncerebral tissues were near 0. Regarding correcting uptakes for C, instead of a universally assumed and applied gamma = -1, corrections should be for a single tissue using its known gamma. An advantageous use of gamma is predicting how C affects image contrast, including where glucose loading is sometimes preferable to fasting.
A potentially useful quantifier of uptake sensitivity to plasma glucose has been defined and values obtained. Correcting uptakes to some standard C requires special care. gamma can help PET clinicians select fasting or loading to achieve glucose levels for optimum contrast.
Purpose: The potential for improving the diagnostic performance of static positron imaging tomography (PET) by judiciously choosing optimum post-injection imaging times is investigated.
Procedures: ...Dynamic and whole-body scan data, from 2-deoxy-2-
18Ffluoro-D-glucose (FDG) oncological studies, are analyzed for changing standardized uptake value (SUV) behavior with increasing post-injection times at either single- or multiple-bed positions. Model-based interpretations address d(SUV)/dt, shown to correlate with SUV, and the contrast ratio for a tumor and its surroundings. A method for correcting measurements to a standardized time is given.
Results: Both data and model-based equations suggest that starting data acquisition later than the average 55 ± 15 (SD) minutes post-injection reported in the FDG literature can improve contrast ratios. Considerations for choosing an optimum time from a clinical standpoint are listed.
Conclusions: It is concluded that the appropriate time for each particular protocol can be found with the aid of the information presented here. True optimization, however, remains a complex issue. (Mol Imag Biol 2002;4:238–244)
PDF
