N.m.r. imaging of intact biological systems

Internal images of structured objects may be obtained with n.m.r. by labelling component parts with different magnetic field strengths and therefore recognizably different n.m.r. frequencies. A linear field gradient generates a one-dimensional projection of nuclear density and a variety of techniques are employed to manipulate this one-dimensional probe to yield internal images in two and three dimensions. In the past few years, n.m.r. imaging, sometimes also called zeugmatography or spin mapping, has been applied progressively to provide proton images of small phantoms, fruit, vegetables and small animals, and finally to in vivo imaging of the human body; it promises to provide a valuable means of interior investigation of intact biological systems generally. For medical imaging the method is non-invasive, does not use ionizing radiations, appears to be without hazard and penetrates bony cavities without attenuation. Furthermore, other n.m.r. parameters, for example, relaxation times and fluid flow, may also be mapped; there is evidence that the relaxation times from tumours are significantly longer than those from corresponding normal tissue. Effort to date has mostly been concentrated on proton n.m.r., but some work has been done with other nuclei. Three examples are shown of n.m.r. images of intact biological systems: a fruit, an animal and a human system. The discussion includes the quantitative nature of the images, tissue discrimination, the relation between the resolution in the image and image acquisition time, attenuation and phase shift of the r.f. field in the biological tissue, and magnets suitable for n.m.r. imaging. In principle, all conventional n.m.r. techniques can be combined with n.m.r. methods in order to investigate heterogeneous systems. Overhauser imaging is briefly discussed.     

The Wellcome Foundation lecture, 1984. Nuclear magnetic resonance imaging in medicine: medical and biological applications and problems

From early biological work and the first T1 nuclear magnetic resonance (n.m.r.) animal image in 1974, whole-body patient images, by using a two-dimensional Fourier transform method were achieved in Aberdeen in 1980 with a 0.04 T vertical resistive magnet. Different pulse sequences produce images dependent by different amounts on proton density, T1 and T2, and for clinical work it is advantageous to use more than one pulse sequence to image pathology. The slow improvement of spatial resolution with increasing standing magnetic field strength is discussed and information on the T1 and T2 contrast dependence is reviewed: it suggests that the gains from high fields may be less than believed hitherto. Electrocardiogram gating can be used to produce moving images of the beating heart; blood flow can be imaged and surface radiofrequency coils are used for improved detail. N.m.r. imaging has considerable potential for studying response to therapy; mental states and dementia; tissue generation; discriminating body fat and body fluids. Other nuclei such as 23Na can be imaged and the potential to image fluorine-labelled pharmaceuticals could be very exciting; n.m.r. contrast agents are now being developed. Images formed from T1 values measured for each pixel are very useful for diagnosis, but the numerical values themselves are less valuable for distinctive pathological identification. With 15 companies manufacturing n.m.r. imagers and over 200 in use in hospitals, the technique is rapidly becoming established in diagnostic clinical practice and some typical uses are presented.     

Progress in n.m.r. zeugmatography imaging

Applications of nuclear magnetic resonance (n.m.r.) zeugmatographic imaging to medical diagnosis and to medical, physiological, and biological research require the development of appropriate imaging instrumentation and ancillary techniques, as well as an understanding of the biological significance of the imaging results. A whole body imaging system, relying primarily upon reconstruction from projections, is under development in the expectation that the reconstruction approach will be the most practical one for many purposes. In addition, injectable magnetic reagents that can selectively change tissue water relaxation times and image contrast are under development so as to increase the specificity and versatility of the measurements. If very high magnetic fields are employed, 31P n.m.r. zeugmatography may be practical at very low resolution for human diagnostic studies and for experiments on perfused organs and small animals. Preliminary images, showing the spatial distributions of different phosphorus metabolites in the compartments of test objects, have been obtained at 146 MHz by reconstruction techniques.     

Some biophysical applications of motional contrast in n.m.r. microscopy

The principal advantage of the n.m.r. imaging method lies in the specific contrasts which are available. In this work we describe the use of velocity and diffusion contrast methods in biophysical applications and at microscopic spatial resolution. In the first example, involving water-protein interactions, the relationship between water self-diffusion and water concentration, as measured using pulsed gradient spin echo n.m.r., is shown. It is demonstrated that this relationship can be used to provide a water concentration image. The result is compared with the conventional proton density and transverse relaxation maps. The next example concerns the use of dynamic n.m.r. microscopy to obtain water diffusion and velocity maps for wheat grain in vivo. Finally we suggest how the method may be used in the study of polymer-water interactions in an unusual adjunct to conventional polymer self-diffusion studies.     

A new nuclear magnetic resonance property of lung

Inflated lung has a nuclear magnetic resonance (NMR) free-induction decay (FID) which is short compared with that of collapsed lung and those of other body tissues. An almost identically short FID is obtained from a slurry of 5-micron alumina particles in water. Interfaces between air and water in lung and between alumina and water in the slurry appear to be the source of spatial internal magnetic inhomogeneities which produce NMR line broadening and the short FID. Paired images that included lung, taken with paired symmetric and asymmetric NMR spin-echo sequences, permit the generation of an image, by subtraction, of the lung isolated from surrounding tissue. These new lung images are neither proton density, T1 (spin-lattice relaxation time), nor T2 (spin-spin relaxation time) images. They complement current NMR images and provide information about regional lung inflation. This previously unrecognized NMR property of lung tissue has potential application in NMR imaging, in quantitative determination of lung water and its distribution, and in the quantitation of regional lung inflation.     

N.m.r. relaxation and images of human breast tumours in vitro

It is found that fat and non-fatty tissue in dissected samples of the mamma differ in their T1/T2 ratios. This opens the possibility of locating tumours by n.m.r. imaging, because they have a lower fat content than their surroundings. By means of a sensitive point method, samples were scanned with a resolution of about 0.4 mm X 0.4 mm. The similarity between the shape of a tumour in an n.m.r. and in an X-ray image of a thin section of mamma tissue is quite convincing.     

Magnetic resonance microscopy at 14 Tesla and correlative histopathology of human brain tumor tissue

Magnetic Resonance Microscopy (MRM) can provide high microstructural detail in excised human lesions. Previous MRM images on some experimental models and a few human samples suggest the large potential of the technique. The aim of this study was the characterization of specific morphological features of human brain tumor samples by MRM and correlative histopathology. We performed MRM imaging and correlative histopathology in 19 meningioma and 11 glioma human brain tumor samples obtained at surgery. To our knowledge, this is the first MRM direct structural characterization of human brain tumor samples. MRM of brain tumor tissue provided images with 35 to 40 μm spatial resolution. The use of MRM to study human brain tumor samples provides new microstructural information on brain tumors for better classification and characterization. The correlation between MRM and histopathology images allowed the determination of image parameters for critical microstructures of the tumor, like collagen patterns, necrotic foci, calcifications and/or psammoma bodies, vascular distribution and hemorrhage among others. Therefore, MRM may help in interpreting the Clinical Magnetic Resonance images in terms of cell biology processes and tissue patterns. Finally, and most importantly for clinical diagnosis purposes, it provides three-dimensional information in intact samples which may help in selecting a preferential orientation for the histopathology slicing which contains most of the informative elements of the biopsy. Overall, the findings reported here provide a new and unique microstructural view of intact human brain tumor tissue. At this point, our approach and results allow the identification of specific tissue types and pathological features in unprocessed tumor samples.     

Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image.

A single abdominal cross-sectional computerized axial tomography and magnetic resonance image is often obtained in studies examining adipose tissue (AT) distribution. An abdominal image might also provide additional useful information on total body skeletal muscle (SM) and AT volumes with related physiological insights. We therefore investigated the relationships between abdominal SM and AT areas from single images and total body component volumes in a large and diverse sample of healthy adult subjects. Total body SM and AT volumes were derived by whole body multislice magnetic resonance imaging in 123 men [age (mean +/- SD) of 41.6 +/- 15.8 yr; body mass index of 25.9 +/- 3.4 kg/m(2)] and 205 women (age of 47.8 +/- 18.7 yr; body mass index of 26.7 +/- 5.6 kg/m(2)). Single abdominal SM and AT slice areas were highly correlated with total body SM (r = 0.71-0.92; r = 0.90 at L(4)-L(5) intervertebral space) and AT (r = 0.84-0.96; r = 0.94 at L(4)-L(5) intervertebral space) volumes, respectively. R(2) increased by only 5.7-6.1% for SM and 2.7-4.4% for AT with the inclusion of subject sex, age, ethnicity, scanning position, body mass index, and waist circumference in the model. The developed SM and AT models were validated in an additional 49 subjects. To achieve equivalent power to a study measuring total body SM or AT volumes, a study using a single abdominal image would require 17-24% more subjects for SM and 6-12% more subjects for AT. Measurement of a single abdominal image can thus provide estimates of total body SM and AT for group studies of healthy adults.     

Image reconstruction of optical attenuation coefficient variation in biological tissues

A procedure for non-invasive imaging of the optical attenuation coefficient variation of in vivo thick organs/tissues is developed. The laser back-scattered surface profiles at various locations of human forearm, by multi-probe reflectometer, are measured. These profiles are matched by iterative procedure, with that as obtained by Monte Carlo simulation and the corresponding values of attenuation coefficient (equal to the sum of absorption and reduced scattering coefficients) are determined. By interpolation of this data a 100 x 100 grid is constructed and after median filtering of this data a color-coded image of the variability of the optical attenuation coefficient of the forearm is obtained. These images in different subjects show variation due to change in overall tissue composition and blood pooling. This non-invasive imaging procedure may help in identifying the diseased affected regions in healthy tissues and in application of photodynamic therapy.     

Imaging brain tissue slices with terahertz near-field microscopy

Photoconductive antenna microprobe (PCAM)-based terahertz (THz) near-field imaging technique is promising for biomedical detection due to its excellent biocompatibility and high resolution; yet it is limited by its imaging speed and the difficulty in the control of the PCAM tip-sample separation. In this work, we successfully realized imaging of mouse brain tissue slices using an improved home-built PCAM-based THz near-field microscope. In this system, the imaging speed was enhanced by designing and applying a voice coil motor-based delay-line. The tip-sample separation control was implemented by developing an image analysis-based technique. Compared with conventional PCAM-based THz near-field systems, our improved system is 100 times faster in imaging speed and the tip-sample separation can be controlled to a few micrometers (e.g., 3 μm), satisfying the requirements of THz near-field imaging of biological samples. It took about ~30 min (not the tens of hours it took to acquire the same kind of image previously) to collect a THz near-field image of brain tissue slices of BALb/c mice (500 μm × 500 μm) with pixel size of 20 μm × 20 μm. The results show that the mouse brain slices can be properly imaged and different regions in the slices (i.e., the corpus callosum region and the cerebrum region) can be identified unambiguously. Evidently, the work demonstrated here provides not only a convincing example but a useful technique for imaging biological samples with THz near-field microscopy. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2741, 2019.     

Effect of head-down tilt on brain water distribution

Vascular and tissue fluid dynamics in the microgravity of space environments is commonly simulated by head-down tilt (HDT). Previous reports have indicated that intracranial pressure and extracranial vascular pressures increase during acute HDT and may cause cerebral edema. Tissue water changes within the cranium are detectable by T2 magnetic resonance imaging. We obtained T2 images of sagittal slices from five subjects while they were supine and during -13 degrees HDT using a 1.5-Tesla whole-body magnet. The analysis of difference images demonstrated that HDT leads to a 21% reduction of T2 in the subarachnoid cerebrospinal fluid (CSF) compartment and a 11% reduction in the eyes, which implies a reduction of water content; no increase in T2 was observed in other brain regions that have been associated with cerebral edema. These findings suggest that water leaves the CSF and ocular compartments by exudation as a result of increased transmural pressure causing water to leave the cranium via the spinal CSF compartment or the venous circulation.     

Experimental considerations in implementing a whole body multiple sensitive point nuclear magnetic resonance imaging system

The multiple sensitive point technique on n.m.r. imaging is discussed in terms of the mode of n.m.r. excitation and detection, provision of field gradients and the methods of data processing. The design criteria of an instrument to implement this and related imaging methods at whole body size are described and particular attention is paid to techniques employed to increase the versatility and ease of use of the apparatus.     

Estimating whole body intermuscular adipose tissue from single cross-sectional magnetic resonance images.

Intermuscular adipose tissue (IMAT), a novel fat depot linked with metabolic abnormalities, has been measured by whole body MRI. The cross-sectional slice location with the strongest relation to total body IMAT volume has not been established. The aim was to determine the predictive value of each slice location and which slice locations provide the best estimates of whole body IMAT. MRI quantified total adipose tissue of which IMAT, defined as adipose tissue visible within the boundary of the muscle fascia, is a subcomponent. Single-slice IMAT areas were calculated for the calf, thigh, buttock, waist, shoulders, upper arm, and forearm locations in a sample of healthy adult women, African-American [n = 39; body mass index (BMI) 28.5 +/- 5.4 kg/m2; 41.8 +/- 14.8 yr], Asian (n = 21; BMI 21.6 +/- 3.2 kg/m2; 40.9 +/- 16.3 yr), and Caucasian (n = 43; BMI 25.6 +/- 5.3 kg/m2; 43.2 +/- 15.3 yr), and Caucasian men (n = 39; BMI 27.1 +/- 3.8 kg/m2; 45.2 +/- 14.6 yr) and used to estimate total IMAT groups using multiple-regression equations. Midthigh was the best, or near best, single predictor in all groups with adjusted R2 ranging from 0.49 to 0.84. Adding a second and third slice further increased R2 and reduced the error of the estimate. Menopausal status and degree of obesity did not affect the location of the best single slice. The contributions of other slice locations varied by sex and race, but additional slices improved predictions. For group studies, it may be more cost-effective to estimate IMAT based on one or more slices than to acquire and segment for each subject the numerous images necessary to quantify whole body IMAT.     

Safe common agents for improved NMR contrast

As nuclear magnetic resonance imaging techniques have developed, a need for agents which can enhance and improve the natural tissue relaxation time differences has become apparent. Especially valuable would be agents that differentially alter NMR images in a manner related to tissue physiology and disease processes. Sophisticated para-magnetic and free radical contrast agents will be discussed in other papers in this issue. However, in this report, some common agents which are currently used in research and in human clinical studies for other purposes, but which can alter NMR contrast will be discussed. These agents include olive oil, estrogen hormones, diuretics, ethanol, glycerin, and dimethyl sulfoxide. Measurements of their relative effects on T1 and T2 of normal and cancerous breast tissues, a variety of body organs, and brain are presented. Some of these agents may have immediate practical applications in human NMR imaging studies.     

Automated classification of atherosclerotic plaque from magnetic resonance images using predictive models

The information contained within multicontrast magnetic resonance images (MRI) promises to improve tissue classification accuracy, once appropriately analyzed. Predictive models capture relationships empirically, from known outcomes thereby combining pattern classification with experience. In this study, we examine the applicability of predictive modeling for atherosclerotic plaque component classification of multicontrast ex vivo MR images using stained, histopathological sections as ground truth. Ten multicontrast images from seven human coronary artery specimens were obtained on a 9.4 T imaging system using multicontrast-weighted fast spin-echo (T1-, proton density-, and T2-weighted) imaging with 39-mum isotropic voxel size. Following initial data transformations, predictive modeling focused on automating the identification of specimen's plaque, lipid, and media. The outputs of these three models were used to calculate statistics such as total plaque burden and the ratio of hard plaque (fibrous tissue) to lipid. Both logistic regression and an artificial neural network model (Relevant Input Processor Network-RIPNet) were used for predictive modeling. When compared against segmentation resulting from cluster analysis, the RIPNet models performed between 25 and 30% better in absolute terms. This translates to a 50% higher true positive rate over given levels of false positives. This work indicates that it is feasible to build an automated system of plaque detection using MRI and data mining.     

A study to determine the impact of IMPT optimization techniques on prostate synthetic CT image sets dose comparison against CT image sets

BackgroundThe objective of this study is to determine the impact of intensity modulated proton therapty (IMPT) optimization techniques on the proton dose comparison of commercially available magnetic resonance for calculating attenuation (MRCA T) images, a synthetic computed tomography CT (sCT) based on magnetic resonance imaging (MRI) scan against the CT images and find out the optimization technique which creates plans with the least dose differences against the regular CT image sets.Material and methodsRegular CT data sets and sCT image sets were obtained for 10 prostate patients for the study. Six plans were created using six distinct IMPT optimization techniques including multi-field optimization (MFO), single field uniform dose (SFUD) optimization, and robust optimization (RO) in CT image sets. These plans were copied to MRCA T, sCT datasets and doses were computed. Doses from CT and MRCA T data sets were compared for each patient using 2D dose distribution display, dose volume histograms (DVH), homogeneity index (HI), conformation number (CN) and 3D gamma analysis. A two tailed t-test was conducted on HI and CN with 5% significance level with a null hypothesis for CT and sCT image sets.ResultsAnalysis of ten CT and sCT image sets with different IMPT optimization techniques shows that a few of the techniques show significant differences between plans for a few evaluation parameters. Isodose lines, DVH, HI, CN and t-test analysis shows that robust optimizations with 2% range error incorporated results in plans, when re-computed in sCT image sets results in the least dose differences against CT plans compared to other optimization techniques. The second best optimization technique with the least dose differences was robust optimization with 5% range error.ConclusionThis study affirmatively demonstrates the impact of IMPT optimization techniques on synthetic CT image sets dose comparison against CT images and determines the robust optimization with 2% range error as the optimization technique which gives the least dose difference when compared to CT plans.     

Water Selective Imaging and bSSFP Banding Artifact Correction in Humans and Small Animals at 3T and 7T,Respectively

Introduction

The purpose of this paper is to develop an easy method to generate both fat signal and banding artifact free 3D balanced Steady State Free Precession (bSSFP) images at high magnetic field.

Methods

In order to suppress fat signal and bSSFP banding artifacts, two or four images were acquired with the excitation frequency of the water-selective binomial radiofrequency pulse set On Resonance or shifted by a maximum of 3/4TR. Mice and human volunteers were imaged at 7T and 3T, respectively to perform whole-body and musculoskeletal imaging. “Sum-Of-Square” reconstruction was performed and combined or not with parallel imaging.

Results

The frequency selectivity of 1-2-3-2-1 or 1-3-3-1 binomial pulses was preserved after (3/4TR) frequency shifting. Consequently, whole body small animal 3D imaging was performed at 7T and enabled visualization of small structures within adipose tissue like lymph nodes. In parallel, this method allowed 3D musculoskeletal imaging in humans with high spatial resolution at 3T. The combination with parallel imaging allowed the acquisition of knee images with ~500μm resolution images in less than 2min. In addition, ankles, full head coverage and legs of volunteers were imaged, demonstrating the possible application of the method also for large FOV.

Conclusion

In conclusion, this robust method can be applied in small animals and humans at high magnetic fields. The high SNR and tissue contrast obtained in short acquisition times allows to prescribe bSSFP sequence for several preclinical and clinical applications.     

Colorization and automated segmentation of human T2 MR brain images for characterization of soft tissues

Characterization of tissues like brain by using magnetic resonance (MR) images and colorization of the gray scale image has been reported in the literature, along with the advantages and drawbacks. Here, we present two independent methods; (i) a novel colorization method to underscore the variability in brain MR images, indicative of the underlying physical density of bio tissue, (ii) a segmentation method (both hard and soft segmentation) to characterize gray brain MR images. The segmented images are then transformed into color using the above-mentioned colorization method, yielding promising results for manual tracing. Our color transformation incorporates the voxel classification by matching the luminance of voxels of the source MR image and provided color image by measuring the distance between them. The segmentation method is based on single-phase clustering for 2D and 3D image segmentation with a new auto centroid selection method, which divides the image into three distinct regions (gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using prior anatomical knowledge). Results have been successfully validated on human T2-weighted (T2) brain MR images. The proposed method can be potentially applied to gray-scale images from other imaging modalities, in bringing out additional diagnostic tissue information contained in the colorized image processing approach as described.     

First biological images with high-energy proton microscopy

High-energy proton microscopy provides unique capabilities in penetrating radiography including the combination of high spatial resolution and field-of-view, dynamic range of density for measurements, and reconstructing density variations to less than 1% inside volumes and in situ environments. We have recently proposed to exploit this novel proton radiography technique for image-guided stereotactic particle radiosurgery. Results of a first test for imaging biological and tissue-equivalent targets with high-energy (800 MeV) proton microscopy are presented here. Although we used a proton microscope setup at ITEP (Moscow, Russia) optimized for fast dynamic experiments in material research, we could reach a spatial resolution of 150 μm with approximately 10¹⁰ protons per image. The potential of obtaining high-resolution online imaging of the target using a therapeutic proton beam in the GeV energy region suggests that high-energy proton microscopy may be used for image-guided proton radiosurgery.