Imaging biomarkers, quantitative imaging, and bioengineering

Imaging biomarkers define objective characteristics extracted from medical images that are related to normal biological processes, diseases, or the response to treatment. To develop an imaging biomarker, it is necessary to carry out a series of steps to validate its relation with the reality studied and to check its clinical and technical validity. This process includes defining tests for the concepts and mechanisms; obtaining standardized and optimized anatomic, functional, and molecular images; analyzing the data with computer models; displaying data appropriately; obtaining the appropriate statistic measures; and conducting tests on the principle, efficacy, and effectiveness. In this article, we aim to explain the steps that must be established to enable biomarkers to be correctly applied, from their theoretical conception to their clinical implementation. To this end, we use the evaluation of angiogenesis in articular cartilage as an example.     

Dementia, quantitative neuroimaging, and apolipoprotein E genotype

BACKGROUND AND PURPOSE: Quantitative MR imaging differences in an elderly population of subjects with various clinical disorders (including dementia, particularly Alzheimer's disease and vascular dementia) and disorders of mild cognitive impairment were examined. Potential quantitative MR differences were assessed by presence or absence of the apolipoprotein E (APOE) epsilon4 allele and by level of cognitive deficit. METHODS: One hundred eighty subjects with a diagnosis of dementia or other clinical disorders were identified from an eligible population of 5,677 elderly individuals. Age, duration of disease, and head size (where appropriate) were considered as covariates. APOE genotype was determined by polymerase chain reaction using buccal material. Axial and coronal intermediate- and T2-weighted MR images were quantified using a multispectral segmentation algorithm. Cognitive status was assessed by means of a modified Mini-Mental Status Examination. RESULTS: All types of dementing illness showed significant volume reductions in the majority of structures examined, particularly in the total brain, hippocampus, and white and gray matter, and increased CSF and ventricular volumes. Subjects with mild cognitive impairment showed fewer atrophic changes but were still distinguishable from the 24 control subjects. Presence of an epsilon4 allele was associated with smaller hippocampal volume in subjects with Alzheimer's disease and vascular dementia within just 1 year of disease onset. For other analyses, atrophy related to the presence of the epsilon4 allele disappeared after controlling for age and length of disease. CONCLUSION: The effects of the epsilon4 allele on brain morphology may be subtly expressed early in the development of dementia, but do not specifically affect cerebral atrophy thereafter. Cognitive impairment is associated with atrophy irrespective of diagnosis and presence of epsilon4.     

Fractional quantitative computed tomography for bone mineral density evaluation: accuracy, precision, and comparison to quantitative computed tomography

OBJECTIVE: To evaluate bone mineral density considering its distribution, fractional quantitative computed tomography (fQCT) was designed and verified. METHODS: Quantitative computed tomography (QCT) was performed at 64 areas in 10 swine long bones. Fractional quantitative computed tomography was measured at the identical areas as the proportion of pixels showing a bone density higher than 130 mg/mL equivalent. All target areas were extracted and incinerated to measure apparent ash bone density. Based on standard references, the accuracy and precision of fQCT were evaluated and the results were compared with conventional QCT results. RESULTS: The correlation coefficient between fQCT and apparent ash bone density was 0.843 (P < 0.0001). The fQCT showed good correlation with volume fraction (r = 0.88, P < 0.0001). The coefficient of variation of fQCT was 0.42%. The fQCT revealed higher accuracy and precision than the results of QCT. CONCLUSION: Fractional quantitative computed tomography was designed and verified as a reliable method to measure bone mineral density.     

Scatter, spatial resolution, and quantitative recovery in high resolution SPECT.

The potential use of single photon emission CT (SPECT) for quantification depends on its physical performance characteristics. We investigated the performance of a high resolution four-head brain SPECT scanner (Neuro-Spect; Summit/Hitachi). With an attenuation coefficient of 0.11 cm-1 and the Chang correction method, the calibration factor of the scanner was 515 (cpm/ml)/(microCi/ml) and showed only a minimal but systematic dependence on object size. Without scatter, the resolution was 4.7 mm (full width at half-maximum); in a scatter medium, the resolution was 5.3-10.0 mm with high resolution collimation and 7.7-18.8 mm with general purpose collimation, depending on filtering. A recovery coefficient of close to 100% was measured in the center of spheres with a size of at least 20 mm placed in a cylindrical water-filled phantom. In lesions of this size, scatter was 20%. We conclude from our measurements that the investigated high resolution SPECT offers significant improvements in resolution, scatter, and recovery, which will improve both the quality of brain studies and the measurement of quantitative parameters such as the cortex/white matter ratio.     

Fluorescence spectrometry based chromaticity mapping,characterization, and quantitative assessment of dental caries

PurposeDental caries detection, especially the accurate detection of early caries, facilitates prompt interventions. It is reasonably common to use fluorescence imaging for classification and evaluation of caries, but lacks a quantitative, precise and easy-to-use characterization for practical applications. In this study a quantitative approach for caries stage detection by correlating caries spectral and chromatic features was examined.MethodsA 405 nm LED light source was used as the excitation source. A hyperspectral imaging camera is employed to collect 336 spectral data of different caries stages. Four critical intervals for different stages of caries were extracted by fluorescence spectral features. The mapping relationship between caries spectral and chromatic features was established by Fast Formula Fitting (FFF) and Neural Network Fitting (NNF) methods.ResultsThe 470–780 nm spectral power distribution was proved to be the best matching color waveband guiding the selection of filters in future instrument development. The correlation coefficients for the two fitting methods were 0.990 and 0.999, respectively. Both methods achieved caries stage prediction at the pixel level with high accuracy using color information. The visualization region in the chromaticity diagram was created.ConclusionsThis quantitative method enables accurate prediction of caries on the entire tooth surface and facilitates the development of portable and low-cost caries detection instruments.     

Posttransplant renal rejection: comparison of quantitative scintigraphy, US, and MR imaging

Accuracy of ultrasonography (US), quantitative scintigraphy, and magnetic resonance (MR) imaging in diagnosis of acute renal allograft rejection was studied in 46 patients who underwent renal biopsy. Thirty-three patients had acute rejection; six, cyclosporine nephrotoxicity, as shown by biopsy, clinical findings, and follow-up study; two, acute tubular necrosis; and five, normal biopsy findings and renal function. Accuracy in demonstrating rejection was 72% for US and 75% for scintigraphy, indicating no significant difference between the two. MR imaging was significantly more accurate, reaching a level of 98%. However, accuracy of MR in demonstrating acute tubular necrosis in a larger number of patients is not known, and its accuracy in indicating recurrent glomerulopathy or infectious disease has not been addressed. The definitive role of MR in evaluating posttransplant renal failure is currently not established, but because of its high sensitivity in detecting renal abnormality, MR can be used for cases when results of US or scintigraphy are equivocal or contradict clinical impressions or when biopsy cannot be performed for medical reasons.     

Relationships of cervical, thoracic, and lumbar bone mineral density by quantitative CT

PURPOSE: The purpose of this work was to compare, using quantitative CT (QCT), vertebral bone mineral density (BMD) in the cervical, thoracic, and lumbar spine in healthy volunteers. METHOD: QCT of the vertebral bodies of C2, C5, T12, and L4 was performed on 50 healthy volunteers (25 women, 25 men; mean age 31.7 years). Trabecular BMD analysis was performed at each level. RESULTS: Mean BMDs (mg/cm3 calcium hydroxyapatite) for women and men were highest at C5 (BMD women/men 341.6/300.6 mg/cm3) and C2 (297.2/269.6 mg/cm3) and lowest at T12 (193.1/184.9 mg/cm3) and L4 (186.2/180.1 mg/cm3). The BMD of C2 was statistically significantly different from that of C5, T12, and L4 (p < 0.0001) for both genders. Also, the BMD of C5 differed significantly from that of T12 and L4 (p < 0.0001). The BMD of C5 showed significant gender differences (p = 0.002). Correlation coefficient showed a strong correlation between the BMD of T12 and L4 for both genders (women, r = 0.67; men, r = 0.90). CONCLUSION: Trabecular BMD of C2 and C5 measured by QCT is significantly higher than trabecular BMD of T12 and L4 in nonosteoporotic volunteers of both genders.     

Acute, subacute, and chronic myocardial infarction: quantitative analysis of gadolinium-enhanced MR images

The value of gadolinium enhancement to enable detection of infarcted myocardium at T1-weighted magnetic resonance (MR) imaging was assessed in 84 patients after acute myocardial infarction (AMI). Five healthy subjects served as controls. All patients underwent MR imaging before and 20 minutes after administration of gadopentetate dimeglumine. Contrast enhancement of normal myocardium varied 7% +/- 4 after administration of gadopentetate dimeglumine. Mean intensity ratio after gadolinium enhancement in group 1 (imaging less than 1 week after AMI), group 2 (imaging 1-3 weeks after AMI), and group 3 (imaging 3-6 weeks after AMI) was significantly higher than before gadolinium enhancement. In group 4 (imaging more than 6 weeks after AMI), no significant difference was observed. After gadolinium enhancement, the intensity ratio was abnormally increased in 82% of the MR examinations in group 1, in 62% of group 2, in 58% of group 3, and in 12% of group 4. Gadolinium enhancement improved visualization of myocardial infarction at MR imaging up to 6 weeks after onset of symptoms and had a maximal effect within 1 week after AMI.     

蓝莓花色苷的定量分析与吸收代谢研究进展

花色苷是蓝莓中主要的酚类化合物,具有抗氧化、抗癌、视力保护、改善心血管功能等作用,是蓝莓的主要活性成分之一.但花色苷成分复杂,且体内生物利用度极低,限制了蓝莓花色苷药理功效的发挥.准确检测与定量蓝莓花色苷,分析其在胃肠道消化和体内代谢转化情况,有助于解析花色苷类化合物的有效摄入与功效机制.该文对近年来蓝莓花色苷的定量分...     

In vivo analysis of single, pre- and postprocessing quantitative CT techniques

Measurements of bone mineral using single and dual-energy quantitative computed tomography (CT) are examined in vivo in 108 vertebral bodies scanned on a Siemens DRH scanner. Pre and postprocessing dual-energy techniques are compared. In the range of clinically useful kilovoltage, the choice of beam energy does not make a significant difference to the single-energy bone mineral measurement. Postprocessing dual-energy measurement in vivo shows a statistically significant decrease in the amount of mineral measured compared to single-energy measurements, whereas the preprocessing measurement shows a significant increase.     

Der Nachweis,die Unterscheidung und quantitative Bestimmung zentral wirkender,synthetischer Analgetica,insbesondere des Cliradons im Urin

Ohne ZusammenfassungVortrag anläßlich der Tagung der Deutschen Gesellschaft für gerichtliche und soziale Medizin in München, 1952.     

Transient left ventricular dilation at quantitative stress-rest sestamibi tomography: Clinical, electrocardiographic, and angiographic correlates

BACKGROUND: Few data are available regarding the incidence and significance of transient left ventricular (LV) dilation on stress sestamibi single photon emission computed tomography (SPECT), which is different from thallium-201 studies because images are acquired late after tracer injection. METHODS: We studied 234 patients with ischemic heart disease and interpretable electrocardiograms undergoing stress-rest sestamibi SPECT on separate days. Sestamibi uptake defect extent was quantified on SPECT polar maps. Epicardial and endocardial transient dilation indexes (TDI) were also calculated. RESULTS: According to our normal TDI values, 148 patients (63%) had no dilation and 86 patients (37%) had abnormal endocardial TDI; a global LV dilation (abnormal endocardial and epicardial TDI) was observed in 19 patients (8%). ST-segment depression was more frequent in patients with transient LV dilation (55%) than in those without (36%; P < .01), as were the extent of stress hypoperfusion (13% +/- 12% vs 6% +/- 7% in patients with no dilation; P < .001) and the angiographic severity score (11.4 +/- 5.9 vs 9.2 +/- 3.7; P < .05). At multivariate analysis, stress hypoperfusion was the sole predictor of transient LV dilation. CONCLUSIONS: Transient LV cavity dilation is frequent on stress sestamibi SPECT. Ventricular cavity dilation is more common than global dilation and suggests subendocardial ischemia. It is related to a greater amount of jeopardized myocardium and is strongly associated with electro-cardiographic signs of ischemia.