SPatial REgression Analysis of Diffusion tensor imaging (SPREAD) for longitudinal progression of neurodegenerative disease in individual subjects

Objectives

To develop a novel statistical method for analysis of longitudinal DTI data in individual subjects.

Materials and Methods

The proposed SPatial REgression Analysis of Diffusion tensor imaging (SPREAD) method incorporates a spatial regression fitting of DTI data among neighboring voxels and a resampling method among data at different times. Both numerical simulations and real DTI data from healthy volunteers and multiple sclerosis (MS) patients were used in the study to evaluate this method.

Results

Statistical inference based on SPREAD was shown to perform well through both group comparisons among simulated DTI data of individuals (especially when the group size is smaller than 5) and longitudinal comparisons of human DTI data within the same individual.

Conclusions

When pathological changes of neurodegenerative diseases are heterogeneous in a population, SPREAD provides a unique way to assess abnormality during disease progression at the individual level. Consequently, it has the potential to shed light on how the brain has changed as a result of disease or injury.     

In vivo 31P echo-planar spectroscopic imaging of human calf muscle

Localized phosphorus-31 NMR spectra of human calf muscle in vivo were obtained by means of echo-planar spectroscopic imaging (EPSI) with a 1.5-T whole-body scanner. The technique permits the measurement of two-dimensional 31P SI data at a minimum acquisition time of 2.4 s (8x8 voxels, TR=300 ms). With 9.4 min measurement time (TR=1100 ms, 64 averages) and 25x25x40 mm spatial resolution in vivo the 31P NMR signal-to-noise ratio (S/N) of the phosphocreatine (PCr) resonance was about 45; the multiplets of nucleoside 5'-triphosphates were resolved. Spectral quality permits quantitative assessment of the PCr signal in a measurement time that is shorter by a factor of 2 or more than the minimum measurement time feasible with chemical-shift imaging. In a functional EPSI study with a time resolution of 20.5 s on the calf muscle of volunteers, spectra showed a 40% decrease of the PCr signal intensity (at rest: S/N congruent with12) upon exertion of the muscle.     

An algorithm to estimate anatomical connectivity between brain regions using diffusion MRI

The study of anatomical connectivity is essential for interpreting functional MRI data and for establishing how brain areas are linked together into networks to support higher-order functions. Diffusion-weighted MR images (DWI) and tractography provide a unique noninvasive tool to explore the connectional architecture of the brain. The identification of anatomical circuits associated with a specific function can be better accomplished by the joint application of diffusion and functional MRI. In this article, we propose a simple algorithm to identify the set of pathways between two regions of interest. The method is based upon running deterministic tractography from all possible starting positions in the brain and selecting trajectories that intersect both regions. We compare results from single-fiber tractography using diffusion tensor imaging and from multi-fiber tractography using reduced-encoding persistent angular structure (PAS) MRI on standard DWI datasets from healthy human volunteers. Our results show that, in comparison with single-fiber tractography, the multi-fiber technique reveals additional putative routes of connection. We demonstrate highly consistent results of the proposed technique over a cohort of 16 healthy subjects.     

Assessment of pulmonary air trapping and obstruction in expiration: an experimental MRI study

PURPOSE: The aim of this experimental study was to evaluate the potential of a simple expiration technique by means of magnetic resonance imaging (MRI) in an animal model to detect pulmonary air-trapping areas after artificial bronchial obstruction. MATERIAL AND METHODS: Sixteen pigs were evaluated by means of a modified T1-weighted FLASH with fat saturation in respiratory arrest (TR=4.6 ms, TE=1.8 ms, alpha=10 degrees, S.D.=3-5 mm). A measurement of the signal intensity (SI) in the peripheral lung tissue was made in both inspiration and expiration before and after inhalation of 2 ml of 0.5% acetylcholine to simulate a bronchial obstruction. A final measurement of the lung SI was also made after bronchospasmolytic induction through salbutamol (beta2-mimetic bronchodilator). RESULTS: In expiration, a mean SI increase in peripheral lung tissue of about 183% was seen in comparison to inspiration (mean SI increase of 11-32). After inhalation of 0.5% acetylcholine, the expirational signal increase in peripheral lung tissue was only 114% of the original SI. The expirational signal homogeneity decreased after inhalation of acetylcholine. After inhalation of salbutamol, the lung tissue signal elevation in expiration was 193%. CONCLUSION: We interpret the low expiratory signal elevation after acetylcholine inhalation as a result of an air-trapped bronchial constriction in certain areas. The simple expiratory technique in an animal model showed that it is suitable to demonstrate obstructive air trapping using MRI.     

Quantification of venous blood signal contribution to BOLD functional activation in the auditory cortex at 3 T

Most modern techniques for functional magnetic resonance imaging (fMRI) rely on blood-oxygen-level-dependent (BOLD) contrast as the basic principle for detecting neuronal activation. However, the measured BOLD effect depends on a transfer function related to neurophysiological changes accompanying electrical neural activation. The spatial accuracy and extension of the region of interest are determined by vascular effect, which introduces incertitude on real neuronal activation maps. Our efforts have been directed towards the development of a new methodology that is capable of combining morphological, vascular and functional information; obtaining new insight regarding foci of activation; and distinguishing the nature of activation on a pixel-by-pixel basis. Six healthy volunteers were studied in a parametric auditory functional experiment at 3 T; activation maps were overlaid on a high-resolution brain venography obtained through a novel technique. The BOLD signal intensities of vascular and nonvascular activated voxels were analyzed and compared: it was shown that nonvascular active voxels have lower values for signal peak (P<10(-7)) and area (P<10(-8)) with respect to vascular voxels. The analysis showed how venous blood influenced the measured BOLD signals, supplying a technique to filter possible venous artifacts that potentially can lead to misinterpretation of fMRI results. This methodology, although validated in the auditory cortex activation, maintains a general applicability to any cortical fMRI study, as the basic concepts on which it relies on are not limited to this cortical region. The results obtained in this study can represent the basis for new methodologies and tools that are capable of adding further characterization to the BOLD signal properties.     

Validation of optimal DCE-MRI perfusion threshold to classify at-risk tumor imaging voxels in heterogeneous cervical cancer for outcome prediction

Purpose

To classify tumor imaging voxels at-risk for treatment failure within the heterogeneous cervical cancer using DCE MRI and determine optimal voxel's DCE threshold values at different treatment time points for early prediction of treatment failure.

Material and Method

DCE-MRI from 102 patients with stage IB2–IVB cervical cancer was obtained at 3 different treatment time points: before (MRI 1) and during treatment (MRI 2 at 2–2.5 weeks and MRI 3 at 4–5 weeks). For each tumor voxel, the plateau signal intensity (SI) was derived from its time-SI curve from the DCE MRI. The optimal SI thresholds to classify the at-risk tumor voxels was determined by the maximal area under the curve using ROC analysis when varies SI value from 1.0 to 3.0 and correlates with treatment outcome.

Results

The optimal SI thresholds for MRI 1, 2 and 3 were 2.2, 2.2 and 2.1 for significant differentiation between local recurrence/control, respectively, and 1.8, 2.1 and 2.2 for death/survival, respectively.

Conclusion

Optimal SI thresholds are clinically validated to quantify at-risk tumor voxels which vary with time. A single universal threshold (SI = 1.9) was identified for all 3 treatment time points and remained significant for the early prediction of treatment failure.     

Paradoxical uptake of Gd-EOB-DTPA on the hepatobiliary phase in the evaluation of hepatic metastasis from breast cancer: is the “target sign” a common finding?

Purpose

The purpose was to describe magnetic resonance imaging (MRI) findings of breast cancer liver metastasis using gadoxetic acid (Gd-EOB-DTPA) with an emphasis on the added value of the hepatobiliary phase (HBP).

Material and methods

Nine patients with 13 liver metastases were included in the study after the medical records of 29 breast cancer patients who underwent Gd-EOB-DTPA-enhanced MRI between February 2008 and June 2010 were reviewed. The diagnoses of liver metastasis were established by percutaneous liver biopsy or surgery and on the basis of image findings. Two radiologists retrospectively evaluated signal intensity (SI) and sizes of metastases and patterns of enhancement in an HBP. The SI ratio was calculated as the SI of the central hyperintense portion in “target” lesions divided by the SI of nearby normal liver parenchyma on the HBP. We also measured apparent diffusion coefficient (ADC) values from Diffusion Weighted Image (DWI).

Results

Liver metastases were all hypointense [n=13/13 (100%)] on T1-weighted imaging (WI), and many lesions had a “target” appearance with a central high SI and a peripheral low SI rim (47%) on T2WI. Dynamic study showed rim enhancement on the arterial phase (85%) and a “target” appearance, consisting of a central enhancing portion with peripheral washout or hypointense rim, on the HBP (62%). The mean SI ratio was 0.7. The mean ADC value of “target” appearing metastases was 1.25 (×10⁻³ mm²/s; range 1.3–1.6) compared with a mean value of 0.8 (×10⁻³ mm²/s; range 0.8–1.4) in homogeneous defect on the HBP. There was statistically significant difference (P<.05).

Conclusion

Breast cancer liver metastases commonly demonstrated as a peripheral ring enhancement on arterial dominant phase and a target sign with a central round enhancing portion and a peripheral hypointense rim on the HBP.     

Spectroscopic imaging display and analysis.

A system for display of magnetic resonance (MR) spectroscopic imaging (SI) data is described which provides for efficient review and analysis of the multidimensional spectroscopic and spatial data format of this technique. Features include the rapid display of spectra from selected image voxels, formation of spectroscopic images, spectral and image data processing operations, methods for correlating spectroscopic image data with high resolution 1H MR images, and hardcopy facilities. Examples are shown for 31P and 1H spectroscopic imaging studies obtained in human and rat brain.     

Constrained modeling for spectroscopic measurement of bi-exponential spin-lattice relaxation of water in vivo

The (1)H NMR water signal from spectroscopic voxels localized in gray matter contains contributions from tissue and cerebral spinal fluid (CSF). A typically weak CSF signal at short echo times makes separating the tissue and CSF spin-lattice relaxation times (T(1)) difficult, often yielding poor precision in a bi-exponential relaxation model. Simulations show that reducing the variables in the T(1) model by using known signal intensity values significantly improves the precision of the T(1) measurement. The method was validated on studies on eight healthy subjects (four males and four females, mean age 21 +/- 2 years) through a total of twenty-four spectroscopic relaxation studies. Each study included both T(1) and spin-spin relaxation (T(2)) experiments. All volumes were localized along the Sylvian fissure using a stimulated echo localization technique with a mixing time of 10 ms. The T(2) experiment consisted of 16 stimulated echo acquisitions ranging from a minimum echo time (TE) of 20 ms to a maximum of 1000 ms, with a repetition time of 12 s. All T(1) experiments consisted of 16 stimulated echo acquisition, using a homospoil saturation recovery technique with a minimum recovery time of 50 ms and a maximum 12 s. The results of the T(2) measurements provided the signal intensity values used in the bi-exponential T(1) model. The mean T(1) values when the signal intensities were constrained by the T(2) results were 1055.4 ms +/- 7.4% for tissue and 5393.5 ms +/- 59% for CSF. When the signal intensities remained free variables in the model, the mean T(1) values were 1085 ms +/- 19.4% and 5038.8 ms +/- 113.0% for tissue and CSF, respectively. The resulting improvement in precision allows the water tissue T(1) value to be included in the spectroscopic characterization of brain tissue.     

Correlation between metabolite ratios and ADC values of prostate in men with increased PSA level

Proton magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI) were carried out in men with increased prostate-specific antigen (PSA) level. Forty subjects [controls (Group I) and patients (Groups II and III with PSA >20 and 4-20 ng/ml, respectively)] were investigated using endorectal coil at 1.5 T prior to transrectal ultrasound (TRUS)-guided biopsy. Metabolite ratio [citrate/(choline+creatine)] and apparent diffusion coefficient (ADC) were calculated for identical voxels. In patients, voxels that showed lower metabolite ratio showed reduced ADC in the peripheral zone (PZ) of the prostate, and voxels with increased metabolite ratio showed higher ADC. Metabolite ratios were used to predict areas of malignancy if the ratio was <1.4 and if ADC value was <1.17 x 10(-3) mm(2)/s. Patients in Group II had lower metabolite ratio and ADC in the PZ compared to controls and Group III. All 13 were positive for malignancy in MR, while 12 of 13 were positive on TRUS-guided sextant biopsy. In Group III, certain voxels of PZ that showed reduced metabolite ratio also showed lower ADC. A positive correlation was observed between metabolite ratio and ADC. MR predicted areas of malignancy in PZ in 15 of 20 patients; however, only six were positive on TRUS-guided biopsy perhaps due to high false-negative rate of TRUS-guided biopsy. Results show positive correlation between MRSI and DWI and their potential in detection of malignancy, thereby improving the diagnosis especially in patients with PSA level of 4-20 ng/ml.     

水体的温度变化对测定溶解有机物浓度的影响

用激光诱导荧光(LIF)方法研究了水体的温度变化对溶解有机物(DOM)发射荧光强度的影响。随着温度的增加,DOM的荧光强度和水的拉曼散射强度不断降低。在20～75 ℃范围之内,对归一化荧光强度与温度关系曲线进行线性拟合,计算出归一化荧光强度随温度升高的变化梯度平均值为-5.24×10-4 ℃-1,根据归一化荧光强度与浓度的关系,给出了所测DOM的浓度随着温度升高的平均下降速率为-3.45×10-3 (mg·L-1)·℃-1。因此,在这一温度范围内测量时,假设归一化荧光强度不变,则温度变化将引起DOM浓度最大为8.45%的相对变化。     

Improvement of spectral resolution by spectroscopic imaging

We propose to use three-dimensional spectroscopic imaging (SI) to increase the spectral resolution for biological samples for which strong susceptibility effects (or poor magnetic homogeneity) cause significant line broadening. Due to susceptibility effects (or poor field homogeneity) the SI voxel spectra even from a uniform sample are shifted with respect to each other and much less broadened than the total sample spectrum. Realignment of the spectra from individual voxels prior to their coaddition produces a total-volume spectrum with significantly narrower lines.     

Correlation of proton MR spectroscopy and diffusion tensor imaging

Proton magnetic resonance spectroscopy ((1)H-MRS) provides indices of neuronal damage. Diffusion tensor imaging (DTI) relates to water diffusivity and fiber tract orientation. A method to compare (1)H-MRS and DTI findings was developed, tested on phantom and applied on normal brain. Point-resolved spectroscopy (T(R)/T(E)=1500/135) was used for chemical shift imaging of a supraventricular volume of interest of 8 x 8 x 2 cm(3) (64 voxels). In DTI, a segmental spin-echo sequence (T(R)/T(E)=5500/91) was used and slices were stacked to reproduce the slab used in MRS. The spatial distributions of choline and N-acetylaspartate (NAA) correlated to mean fractional anisotropy and apparent diffusion coefficient (ADC) for the inner 6 x 6=36 voxels defined in MRS, most notably NAA and ADC value (r=-.70, P<.00001; correlation across four subjects, 144 data pairs). This is the first association of neuron metabolite contents in volunteers with structure as indicated by DTI.     

基于椭偏光谱仪的石英晶体1310nm处双折射率的精密测量

为了对石英晶体在通讯波段1 310 nm处的双折射率进行精密测量,基于椭偏光谱仪对P和S两方向上偏振光相位差的精密测量原理,在透射模式下,通过对琼斯矩阵的分析,设计了一种精密测量晶体双折射率的方法,并在室温(22℃)下对通讯波段1 310 nm处石英晶体的双折射率进行了精密测量,测量结果和对误差的分析显示,此方法给出的...     

System for determination of ultrasonic wave speeds and their temperature dependence in liquids and in vitro tissues

An interferometric technique capable of accurately measuring wave speed in liquids is reported. The hardware is adapted from a design to measure nonlinear responses of biological tissues to pressure changes (pressure derivatives) and temperature changes (temperature derivatives). It is used with the highly sensitive variable frequency pulsed phase-locked loop (VFPPLL) instrument. The system uses well-understood and well-characterized components and systems. The apparatus covers a temperature range from below 5 degrees C to above 45 degrees C. The system with the high-sensitivity VFPPLL is capable of measurement of wave speed to an uncertainty of less than 0.1%, and changes in wave speed to better than 0.001%. The transducer is an undamped temperature-characterized PZT-5A 500-kHz plate, whose output is corrected for off-resonance operation and for diffraction effects. To test the accuracy of the technique, measurement of ultrasonic compressional wave speed in water at temperatures from 10 degrees C to 45 degrees C are reported, with an estimated uncertainty of 0.07% and a temperature uncertainty of 0.15 degrees C. The agreement between mean values and literature values is better than 0.05%.     

On the effects of gating in diffusion imaging of the brain using single shot EPI.

To reduce image artifacts in diffusion tensor imaging using single shot EPI, cardiac gating may be performed to prevent brain motion induced signal void in the DWI data. In this work the necessity of performing cardiac gating with single shot echo planar imaging has been explored using F statistics of the variance in DWI data. Peripheral measurement of the cardiac cycle has been employed because of its greater convenience, and hence use, compared to ECG gating. Four volunteers have been studied. Six different trigger delays have been evaluated in the range 18-500 ms relative the peripheral pulse wave. Brain motion was found significant in and inferior to the corpus callosum area. A trigger delay of 500 ms was found to be optimal. However, a long delay allows only for one slice per R-R interval. Therefore, a minimum trigger delay may be the best choice in terms of SNR per unit of experiment time.     

微流控芯片系统中测温及控温装置的研制

报道了一种结构简单、成本低、操作方便、应用于微流控芯片系统中温度测量及温度控制的装置。该系统以CCD摄像机、荧光显微镜及图像采集卡构成的非接触荧光指示剂测温装置,实现了微流体空间温度分布测量以及随时间变化的温度测量。提出了以透明氧化铟锡薄膜玻璃作为加热元件,采用PID控制算法的温度控制平台,稳态时温度控制精度可达到±0.1 ℃。采用该测温和控温装置研究了玻璃微流控芯片微通道内溶液温度在空间上和随时间的变化情况,结果表明该方法简单、有效,可达到μm级的空间分辨率和ms级的时间分辨率。     

Apparent diffusion coefficient (ADC) measurements may be more reliable and reproducible than lesion volume on diffusion-weighted images from patients with acute ischaemic stroke-implications for study design

Early ischemic change after stroke can be demonstrated with diffusion-weighted imaging (DWI) and quantified by measuring the apparent diffusion coefficient (ADC) and/or lesion volume. We examined the reliability and reproducibility of lesion volume and ADC measurement on DWI images, and discuss the implications for clinical studies. Using 38 DWI scans from 15 stroke patients, two observers (a physicist and a neuroscience graduate) blind to each other, recorded the lesion volume on DWI sequences, measured the ADC values in this volume and calculated the ratio of ischemic: control ADC (ADCr). One observer repeated his measurements blind to his first, and also examined the effect on lesion volume and ADC of deliberately varying by only one pixel, the outline of the visible boundary of the lesion. The inter and intra-rater reliability were worse for lesion volume than ADC or ADCr measurements: lesion volume, inter-rater coefficient of variation (CoV) 85 +/- 130%, intra-rater CoV 20+/-SD80% (p < 0.05); ADC inter-rater CoV 7.7 +/- SD 19%, intra-rater CoV 0.2 +/- SD 12% (p = NS); and ADCr inter-rater CoV 8 +/- SD27%, intra-rater CoV 0.8 +/- SD73% (p = NS). Altering the position of the outline tracing of the lesion boundary by one pixel altered the measured volumes by 22 +/- SD25% (p < 0.05), but ADC values were altered by only 2.9 +/- SD4.9% and ADCr by 2.7 +/- SD4.8% (p = NS). ADC and ADCr values are more reliable and reproducible than DWI lesion size in acute ischemic stroke because altering where the lesion boundary is measured has a much greater impact on lesion volume than on the ADC or ADCr. This effect is greatest in large lesions.     

Optimization of MR diffusion-weighted imaging acquisitions for pancreatic cancer at 3.0 T

Objectives

To investigate and optimize diffusion-weighted imaging (DWI) acquisitions for pancreatic cancer at 3.0 T.

Methods

Forty-five patients with pancreatic cancer were examined by four DWI acquisitions with b values = 0 and 600 s/mm² at 3.0 T, including breath-holding DWI (BH-DWI), respiratory-triggered DWI (TRIG-DWI), respiratory-triggered DWI with inversion–recovery technique (TRIGIR-DWI), and free-breathing DWI with inversion–recovery technique (FBIR-DWI). Artifacts, contrast ratio (CR), contrast-to-noise ratio (CNR) and apparent diffusion coefficient (ADC) of pancreatic cancer were statistically compared among DWI acquisitions.

Results

TRIGIR-DWI displayed the lowest artifacts and highest CR compared to other DWI acquisitions. CNRs of pancreatic cancer in TRIG-DWI and TRIGIR-DWI were statistically higher than that in FBIR-DWI and BH-DWI. Different ADCs between pancreatic cancer and noncancerous pancreatic tissues were noticed by a paired-samples T test in TRIG-DWI (p = 0.017), TRIGIR-DWI (p = 0.00001) and FBIR-DWI (p = 0.000041).

Conclusions

TRIGIR-DWI may be the optimal acquisition of DWI for pancreatic cancer at 3.0 T.     

Subject-specific changes in brain white matter on diffusion tensor imaging after sports-related concussion

Background and Purpose

Current approaches to diffusion tensor imaging (DTI) analysis do not permit identification of individual-level changes in DTI indices. We investigated the ability of wild bootstrapping analysis to detect subject-specific changes in brain white matter (WM) before and after sports-related concussion.

Materials and Methods

A prospective cohort study was performed in nine high school athletes engaged in hockey or football and six controls. Subjects underwent DTI pre- and postseason within a 3-month interval. One athlete was diagnosed with concussion (scanned within 72 h), and eight suffered between 26 and 399 subconcussive head blows. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in each WM voxel. Bootstrap samples were generated, and a permuted t test was used to compare voxel-wise FA/MD changes in each subject pre- vs. postseason.

Results

The percentage of WM voxels with significant (p<.05) pre–post FA changes was highest for the concussion subject (3.2%), intermediary for those with subconcussive head blows (mean 1.05%±.15%) and lowest for controls (mean 0.28%±.01%). Similarly, the percentage of WM voxels with significant MD changes was highest for the concussion subject (3.44%), intermediary for those with subconcussive head blows (mean 1.48%±.17%) and lowest for controls (mean 0.48%±.05%). Significantly changed FA and MD voxels colocalized in the concussion subject to the right corona radiata and right inferior longitudinal fasciculus.

Conclusions

Wild bootstrap analysis detected significantly changed WM in a single concussed athlete. Athletes with multiple subconcussive head blows had significant changes in a percentage of their WM that was over three times higher than controls. Efforts to understand the significance of these WM changes and their relationship to head impact forces appear warranted.