Accuracy of image registration between MRI and light microscopy in the ex vivo brain

A multistep procedure was developed to register magnetic resonance imaging (MRI) and histological data from the same sample in the light microscopy image space, with the ultimate goal of allowing quantitative comparisons of the two datasets. The fixed brain of an owl monkey was used to develop and test the procedure. In addition to the MRI and histological data, photographic images of the brain tissue block acquired during sectioning were assembled into a blockface volume to provide an intermediate step for the overall registration process. The MR volume was first registered to the blockface volume using a combination of linear and nonlinear registration, and two dimensional (2D) blockface sections were registered to corresponding myelin-stained sections using a combination of linear and nonlinear registration. Before this 2D registration, two major types of tissue distortions were corrected: tissue tearing and independent movement of different parts of the brain, both introduced during histological processing of the sections. The correction procedure utilized a 2D method to close tissue tears and a multiple iterative closest point (ICP) algorithm to reposition separate pieces of tissue in the image. The accuracy of the overall MR to micrograph registration procedure was assessed by measuring the distance between registered landmarks chosen in the MR image space and the corresponding landmarks chosen in the micrograph space. The average error distance of the MR data registered to micrograph data was 0.324±0.277 mm, only 8% larger than the width of the MRI voxel (0.3 mm).     

Ex vivo assessment of polyol coated-iron oxide nanoparticles for MRI diagnosis applications: toxicological and MRI contrast enhancement effects

Polyol synthesis is a promising method to obtain directly pharmaceutical grade colloidal dispersion of superparamagnetic iron oxide nanoparticles (SPIONs). Here, we study the biocompatibility and performance as T2-MRI contrast agents (CAs) of high quality magnetic colloidal dispersions (average hydrodynamic aggregate diameter of 16-27 nm) consisting of polyol-synthesized SPIONs (5 nm in mean particle size) coated with triethylene glycol (TEG) chains (TEG-SPIONs), which were subsequently functionalized to carboxyl-terminated meso-2-3-dimercaptosuccinic acid (DMSA) coated-iron oxide nanoparticles (DMSA-SPIONs). Standard MTT assays on HeLa, U87MG, and HepG2 cells revealed that colloidal dispersions of TEG-coated iron oxide nanoparticles did not induce any loss of cell viability after 3 days incubation with dose concentrations below 50 μg Fe/ml. However, after these nanoparticles were functionalized with DMSA molecules, an increase on their cytotoxicity was observed, so that particles bearing free terminal carboxyl groups on their surface were not cytotoxic only at low concentrations (<10 μg Fe/ml). Moreover, cell uptake assays on HeLa and U87MG and hemolysis tests have demonstrated that TEG-SPIONs and DMSA-SPIONs were well internalized by the cells and did not induce any adverse effect on the red blood cells at the tested concentrations. Finally, in vitro relaxivity measurements and post mortem MRI studies in mice indicated that both types of coated-iron oxide nanoparticles produced higher negative T2-MRI contrast enhancement than that measured for a similar commercial T2-MRI CAs consisting in dextran-coated ultra-small iron oxide nanoparticles (Ferumoxtran-10). In conclusion, the above attributes make both types of as synthesized coated-iron oxide nanoparticles, but especially DMSA-SPIONs, promising candidates as T2-MRI CAs for nanoparticle-enhanced MRI diagnosis applications.     

Tissue contrast enhancement: image reconstruction algorithm and selection of TI in inversion recovery MRI

It is clearly demonstrated that the proper application of the inversion recovery imaging pulse sequence is dependent on the method of image reconstruction and the selection of TI for optimum tissue contrast. There are two methods of 2DFT image reconstruction of IR sequence time-domain raw data. The first is a modulus-image reconstruction algorithm (contrast-obliterating option), and the second is a phase-correction routine for reconstructing "phase-sensitive" true IR-images. The second option generates proper "in-phase" images, retains proper scale of contrast, but can invert the algebraic sign of image-values under certain conditions. A series of "phase-sensitive" and "modulus" reconstructed brain images, obtained with conventional and optimized new IR pulse sequences, are shown to demonstrate these effects. They illustrate the considerable advantages gained, in practical clinical situations, if one generates "phase-sensitive" true IR-images from IR-sequence raw data at optimum TI for tissue contrast enhancement.     

Acoustic characterization of a new trisacryl contrast agent. Part II: Flow phantom study and in vivo quantification

The biocompatible trisacryl particles (TMP) are made of a cross-linked acrylic copolymer. Their inherent acoustic properties, studied for a contrast agent application, have been previously demonstrated in a in vitro Couette device. To measure their acoustic behaviour under circulating blood conditions, the TMP backscatter enhancement was further evaluated on a home-made flow phantom at different TMP doses (0.12-15.6 mg/ml) suspended in aqueous and blood media, and in nude mice (aorta and B16 grafted melanoma). Integrated backscatter (IB) was measured by spectral analysis of the Doppler signals recorded from an ultrasound system (Aplio^®) combined with a 12-MHz probe. Doppler phantom experiments revealed a maximal IB of 17 ± 0.88 dB and 7.5 ± 0.7 dB in aqueous and blood media, respectively. IB measured on mice aorta, in pulsed Doppler mode, confirmed a constant maximal value of 7.29 ± 1.72 dB over the first minutes after injection of a 7.8 mg/ml TMP suspension. Following the injection, a 60% enhancement of intratumoral vascularization detection was observed in power Doppler mode. A preliminary histological study revealed inert presence of some TMP in lungs 8 and 16 days after injection.Doppler phantom experiments on whole blood allowed to anticipate the in vivo acoustic behaviour. Both protocols demonstrated TMP effectiveness in significantly increasing Doppler signal intensity and intratumoral vascularization detection. However, it was also shown that blood conditions seemed to shadow the TMP contrast effect, as compared to in vitro observations. These results encourage further investigations on the specific TMP targeting and on their bio-distribution in the different tissues.     

Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30–60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3–4 days post-treatment.     

Use of capillaries in the construction of an MRI phantom for the assessment of diffusion tensor imaging: demonstration of performance

Although diffusion tensor imaging (DTI) shows great potential for the diagnosis of a variety of pathologies, no consensus for an appropriate assessment standard of DTI exists. This study examined the feasibility of using water-filled arrays of glass capillaries to construct a DTI phantom suitable for making repeated and reproducible measurements required in a quality assessment program. Three phantoms were constructed using arrays of capillaries with three inner diameters (23, 48, and 82 μm). Data were acquired using DTI protocols; the fractional anisotropy (FA), mean apparent diffusion coefficient (ADC) and principal eigenvectors of the diffusion tensors were calculated. This study demonstrated four results: (1) echo-planar images show that susceptibility within the capillary arrays does not lead to substantial differences in precessional frequency in regions containing the arrays and neither do the regions show noticeable image distortion; (2) principal eigenvectors of the diffusion tensors agree to within <10.3° of the array orientations; (3) mean FA values (0.18–0.50) and ADC values (1.40–1.93×10−³ mm²/s) within specified regions of interest are in general agreement with simulations after a simple noise correction; and (4) these array performance characteristics are observable using a typical clinical DTI protocol.     

Analysis of phantom centering positioning on image noise and radiation dose in axial scan type of brain CT

ABSTRACT

This study examined the dose and image quality according to the position change of a human phantom in a CT scan. This study used an MDCT 128 Slice CT Scanner instrument. An axial scan was performed with a 16 cm CTDI phantom of a human phantom, and the dose was measured using a pencil chamber meter. The phantom was scanned 10 cm above and below the isocenter and 15 cm above the right and left. The position of the phantom is indicated by C-0 in the isocenter position, S-10 in the upper 10 cm, I-10 in the lower 10 cm, R-15 in the right 15 cm, and L-15 in the left 15 cm. The test was performed 30 times using the brain CT protocol to calculate the dose and the dose width product (DWP). The acquired images were analyzed using the ImageJ program. Statistical analysis was performed using SPSS with one-way ANOVA (p < .05). The mean DWP values of the CT scanner were C-0 31.97 mGy·cm, S-10 24.52 mGy·cm, I-10 24.28 mGy· cm, R-15 17.95 mGy·cm, and L15 17.6 mGy·cm. Compared to the isocenter (C-0), the DLP values measured at each site were 23.3% for S-10, 24% for I-10, 43.8% for R-15, and 44.9% for L15. A significant difference in the one-way ANOVA statistical process was observed (p>0.05). C-0 was measured to be 7.42 HU, S-10 7.87 HU, I-10 8.4 HU, R-15 117 HU, and L-15 13.6 HU for evaluating the image quality. Compared to C-0, S-10 was 5.39%, I-10 was 13.2%, R-15 was 57.6%, and L-15 was 83.2%. The PSNR for S-10, I-10, R-15, and L-15 was 17.37, 17.5, 16.62, and 16.37 dB, respectively. A good quality image can be obtained by positioning the subject precisely in the isocenter in the axial scan, if possible, because the irradiated dose to the subject is low, which can lead to an increase in noise in image reconstruction.     

Structural effect on degradability and in vivo contrast enhancement of polydisulfide Gd(III) complexes as biodegradable macromolecular MRI contrast agents

The structural effect of biodegradable macromolecular magnetic resonance imaging (MRI) contrast agents, polydisulfide gadolinium (Gd)(III) chelates, on their in vitro degradability, and cardiovascular and tumor imaging were evaluated in mice. Polydisulfide Gd(III) chelates, Gd-DTPA cystamine copolymers (GDCC), Gd-DTPA l-cystine copolymers (GDCP), Gd-DTPA d-cystine copolymers (dGDCP) and Gd-DTPA glutathione (oxidized) copolymers (GDGP), with different sizes and narrow molecular weight distribution were prepared and evaluated both in vitro and in vivo in mice bearing MDA-MB-231 tumor xenografts. GDGP with large steric hindrance around the disulfide bonds had greater T(1) and T(2) relaxivities than GDCC, GDCP and dGDCP. The degradability of the polydisulfide by the endogenous thiols decreased with increasing steric effects around the disulfide bonds in the order of GDCC>GDCP, dGDCP>GDGP. The size and degradability of the contrast agents had a significant impact on vascular contrast enhancement kinetics. The agents with a large size and low degradability resulted in more prolonged vascular enhancement than the agents with a small size and high degradability. It seems that the size and degradability of the agents did not significantly affect tumor enhancement. All agents resulted in significant contrast enhancement in tumor tissue. This study has demonstrated that the vascular enhancement kinetics of the polydisulfide MRI contrast agents can be controlled by their sizes and structures. The polydisulfide Gd(III) chelates are promising biodegradable macromolecular MRI contrast agents for magnetic resonance angiography and cancer imaging.     

A reference agent model for DCE MRI can be used to quantify the relative vascular permeability of two MRI contrast agents

Dynamic Contrast Enhancement (DCE) MRI has been used to measure the kinetic transport constant, K^trans, which is used to assess tumor angiogenesis and the effects of anti-angiogenic therapies. Standard DCE MRI methods must measure the pharmacokinetics of a contrast agent in the blood stream, known as the Arterial Input Function (AIF), which is then used as a reference for the pharmacokinetics of the agent in tumor tissue. However, the AIF is difficult to measure in pre-clinical tumor models and in patients. Moreover the AIF is dependent on the Fahraeus effect that causes a highly variable hematocrit (Hct) in tumor microvasculature, leading to erroneous estimates of K^trans. To overcome these problems, we have developed the Reference Agent Model (RAM) for DCE MRI analyses, which determines the relative K^trans of two contrast agents that are simultaneously co-injected and detected in the same tissue during a single DCE-MRI session. The RAM obviates the need to monitor the AIF because one contrast agent effectively serves as an internal reference in the tumor tissue for the other agent, and it also eliminates the systematic errors in the estimated K^trans caused by assuming an erroneous Hct. Simulations demonstrated that the RAM can accurately and precisely estimate the relative K^trans (R^Ktrans) of two agents. To experimentally evaluate the utility of RAM for analyzing DCE MRI results, we optimized a previously reported multiecho ¹⁹F MRI method to detect two perfluorinated contrast agents that were co-injected during a single in vivo study and selectively detected in the same tumor location. The results demonstrated that RAM determined R^Ktrans with excellent accuracy and precision.     

On- and off-resonance spin-lock MR imaging of normal human brain at 0.1 T: possibilities to modify image contrast

The aim of the present investigation was to determine spin lock (SL) relaxation parameters for the normal brain tissues and thus, to provide basis for optimizing the imaging contrast at 0.1 T. 68 healthy volunteers were included. On-resonance spin lock relaxation time (T_1ρ) and off-resonance spin lock relaxation parameters (T_1ρ^off, M_e/M_o), MT parameters (T_1sat, M_s/M_o), and T₁, T₂ were determined for the cortical gray matter, and for the frontal and parietal white matters. The T_1ρ for the frontal and parietal white matters ranged from 110 to 133 ms and from 122 to 155 ms with locking field strengths from 50 μT to 250 μT, respectively. Accordingly, the values for the gray matter ranged from 127 to 155 ms. With a locking field strength of 50 μT, T_1ρ^off for the frontal and parietal white matters were from 114 to 217 ms and from 126 to 219 ms, and for the gray matter from 136 to 267 ms with the angle between the effective magnetic field (B_eff) and the z-axis (θ) ranging from 60° to 15°, respectively. The T_1ρ of the white and gray matters increased significantly with increasing locking field amplitude (p < 0.001). The T_1ρ^off decreased significantly with increasing θ (p < 0.001). T_1ρ and T_1ρ^off with θ ≥ 30° were statistically significantly shorter in the frontal than in the parietal white matters (p < 0.05). The duration, amplitude and θ of the locking pulse provide additional parameters to optimize contrast in brain SL imaging.     

A variational approach to image registration in dynamic contrast-enhanced MRI of the human kidney

Kidney function can be accessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measurements which yield spatially resolved maps of physiological parameters like perfusion or filtration. The motion of the kidneys during the scan is a dominant limitation of the measurement quality, and image registration is necessary for accurate quantification. We analyzed the feasibility of applying an algorithm, originally developed for multimodal registration, to kidney perfusion time series. The algorithm uses a variational calculation scheme to align the images. In four out of five data sets, kidney motion could be reduced to below the spatial resolution of the images of 1.6 mm while preserving the enhancement pattern of kidney perfusion. Fitting a pharmacokinetic model to the data showed an average reduction of the Akaike fit error of 10% for the registered data, suggesting more stable parameters. We conclude that this image registration algorithm is feasible for correcting kidney motion in renal DCE-MRI.     

Comparison of diffusion tensor,dynamic susceptibility contrast MRI and Tc-Tetrofosmin brain SPECT for the detection of recurrent high-grade glioma

Introduction

Treatment induced necrosis is a relatively frequent finding in patients treated for high-grade glioma. Differentiation by imaging modalities between glioma recurrence and treatment induced necrosis is not always straightforward. This is a comparative study of diffusion tensor imaging (DTI), dynamic susceptibility contrast MRI and ^99mTc-Tetrofosmin brain single-photon emission computed tomography (SPECT) for differentiation of recurrent glioma from treatment induced necrosis.

Methods

A prospective study was made of 30 patients treated for high-grade glioma who had suspected recurrent tumor on follow-up MRI. All had been treated by surgical resection of the tumor followed by standard postoperative radiotherapy with chemotherapy. No residual tumor had been found on brain imaging immediately after the initial treatment. All the patients were studied with dynamic susceptibility contrast brain MRI and, within a week, ^99mTc-Tetrofosmin brain SPECT.

Results

Both ^99mTc-Tetrofosmin brain SPECT and dynamic susceptibility contrast MRI could discriminate between tumor recurrence and treatment induced necrosis with 100% sensitivity and 100% specificity. An apparent diffusion coefficient (ADC) ratio cut-off value of 1.27 could differentiate recurrence from treatment induced necrosis with 65% sensitivity and 100% specificity and a fractional anisotropy (FA) ratio cut-off value of 0.47 could differentiate recurrence from treatment induced necrosis with 57% sensitivity and 100% specificity. A significant correlation was demonstrated between ^99mTc-Tetrofosmin uptake ratio and rCBV (P = 0.003).

Conclusions

Dynamic susceptibility contrast MRI and brain SPECT with ^99mTc-Tetrofosmin had the same accuracy and may be used to detect recurrent tumor following treatment for glioma. DTI also showed promise for the detection of recurrent tumor, but was inferior to both dynamic susceptibility contrast MRI and brain SPECT.     

Use of a modified polysaccharide gel in developing a realistic breast phantom for MRI

A polysaccharide material, TX-151, has been used together with water, NaCl, and Al powder to create a tissue equivalent gel to make a realistic, inexpensive, conveniently moldable, temporally stable tissue equivalent MRI phantom. Various phantom compositions were studied for variations in gelling time and relaxation times. Gd-DTPA added as a T₁ (and T₂) modifier and aluminum powder added to decrease T₂ permitted phantoms to be made with a range of relaxation times comparable to human tissues. We have used this polysaccharide gel to create breast phantoms for testing breast coils and evaluating different MRI imaging sequences available for diagnosis. The breast phantoms consisted of a layer of Crisco, a good model for adipose tissue, surrounding the TX-151 gel. Some of these phantoms were created with a silicone implant encapsulated in the gel to simulate an augmented breast. More sophisticated phantoms can easily be developed by additions of other materials to this polysaccharide gel.     

MRI phantom for tissue simulation with respect to diffusion coefficient and kurtosis - Validation with injection of liposomal theranostics

This study presents gelatine-based and agar-based phantoms with an addition of glycerol, safflower oil, silicone oil and cellulose microcrystalline with a potential to cover the entire range of tissue diffusion coefficients and kurtosis values. Forty types of phantoms were prepared and examined for NMR relaxation times T₁ and T₂ and diffusional metrics D, K and ADC. Wide ranges of values of D (0.0003–0.0031 mm²s⁻¹), K (0.00–7.24) and ADC (0.0002–0.0031 mm²s⁻¹) were observed. Two of the phantoms closely mimic muscle and cortical gray matter with respect to water diffusion parameters. Although many of the presented phantoms display both D and K values within the range of human tissues, they match different tissues with respect to D and K. The imaging results for the gray matter simulating phantom injected with the liposomal solution, bear a resemblance to the particle size effect described in the literature. The phantoms presented in this work are simple in preparation and affordable tissue-simulating materials to be used primarily in development of diffusion kurtosis-based MRI methods and possibly in a preliminary assessment of MRI contrast agents. Further adjustments of the chemical compositions could potentially lead to development of new types of phantoms mimicking diffusional properties of more kinds of soft tissues.     

Combined modified-Dixon and PROPELLER method with low refocusing flip angle for contrast-enhanced fat-suppressed T1-weighted MRI: A prospective cross-sectional study

PurposeTo propose the combined modified-Dixon and PROPELLER sequence with low refocusing flip angle (RFA) and investigate whether this sequence can acquire clinical contrast-enhanced (CE), fat-suppressed T1-weighted (T1W) images of the head and neck.MethodsThe optimal RFA for T1W imaging was investigated in the brain of a healthy volunteer. The motion artifacts, water–fat separation error, contrast ratio (CR), and comprehensive quality were evaluated through comparison with a standard Cartesian modified-Dixon sequence in 50 patients. Two radiologists independently scored motion artifacts and water–fat separation error using a 4-point scale (1, unacceptable; 4, excellent) and comprehensive quality using a 5-point scale (1, substantially inferior; 5, substantially superior). The CR between CE lesions and non-CE muscle was calculated.ResultsThe optimal RFA of 40° was determined. In the motion artifact assessment, ratings of 3 or 4 points were assigned to 83% (observer-1, 42/50; observer-2, 41/50) and 99% (50/50; 49/50) of cases for the standard and proposed sequences, respectively (p < 0.001; p < 0.001). For the water–fat separation error assessment, ratings of 3 or 4 points were assigned to 100% (50/50; 50/50) and 97% (48/50; 49/50) of cases, respectively (p < 0.001; p = 0.02). In comprehensive evaluation, the proposed sequence was equal, slightly superior, or substantially superior to the standard sequence in 85% (39/50; 46/50). The CR was significantly higher with the proposed sequence [2.27 (1.99–2.97) vs. 2.08 (1.88–2.42), p < 0.001].ConclusionThe proposed sequence acquired stable fat-suppressed CE T1W images without motion artifacts and yielded superior overall image quality compared with the standard sequence.     

A data post-processing protocol for dynamic MRI data to discriminate brain activity from global physiological effects

All fMRI techniques measure stimulus induced focal metabolic and physiological changes in activated brain areas. During the entire fMRI experiment it is necessary to maintain the general physiological condition of the subject as stable as possible. This is not always an easy task. The typical block design in standard fMRI experiments minimizes most of the problems related with these general physiological changes. However in some fMRI experiments, like pharmacological MRI, the experimental setup makes the use of a blocked design impossible. Therefore signal correction algorithms have been developed to correct for these physiological signal instabilities. These algorithms often require elaborate calculation efforts and the data interpretation is often very difficult if no prior knowledge on the nature of the changes exists.In this work we present an algorithm, which has the advantage of being low in calculation effort and the resulting data after correction are easy to interpret. It makes use of a datafit between the general physiological and focal activation related signal changes to eliminate the generalized effects. This algorithm has been tested on simulated and experimentally obtained signal traces suffering both from substantial general signal changes overwhelming the smaller focal activation induced signal changes.     

Measurement of contrast of speckle in and near the image plane

The contrast of a speckle pattern formed by a conventional imaging system has been experimentally investigated. A dip in contrast of the speckle pattern produced near the focal plane and the image plane has been observed. It is also found that the variation of contrast along the optical axis of the imaging system with a hard-edged aperture differs considerably from that with a soft aperture.     

Activity revealed in MRI of multiple sclerosis without contrast agent. A preliminary report

Disease activity in multiple sclerosis is usually accompanied by blood-brain barrier disruption, which can be assessed with contrast-enhanced magnetic resonance imaging (MRI). This paper describes a technique that gives information about disease activity using magnetization transfer MRI. Image combination methods using follow-up scans, like the one presented here, have the potential to show MS lesions that correlate with enhancement.