Rapid, high-resolution, whole-brain, susceptibility-based MRI of multiple sclerosis.

BACKGROUND: Susceptibility-based MRI offers a unique opportunity to study neurological diseases such as multiple sclerosis (MS). In this work, we assessed a three-dimensional segmented echo-planar-imaging (3D-EPI) sequence to rapidly acquire high-resolution T2 -weighted and phase contrast images of the whole brain. We also assessed if these images could depict important features of MS at clinical field strength, and we tested the effect of a gadolinium-based contrast agent (GBCA) on these images. MATERIALS AND METHODS: The 3D-EPI acquisition was performed on four healthy volunteers and 15 MS cases on a 3T scanner. The 3D sagittal images of the whole brain were acquired with a voxel size of 0.55 × 0.55 × 0.55 mm(3) in less than 4 minutes. For the MS cases, the 3D-EPI acquisition was performed before, during, and after intravenous GBCA injection. RESULTS: Both T2-weighted and phase-contrast images from the 3D-EPI acquisition were sensitive to the presence of lesions, parenchymal veins, and tissue iron. Conspicuity of the veins was enhanced when images were obtained during injection of GBCA. CONCLUSIONS: We propose this rapid imaging sequence for investigating, in a clinical setting, the spatiotemporal relationship between small parenchymal veins, iron deposition, and lesions in MS patient brains.

Prevalence and co-infection of Toxoplasma gondii and Neospora caninum in Apodemus sylvaticus in an area relatively free of cats.

The protozoan parasite Toxoplasma gondii is prevalent worldwide and can infect a remarkably wide range of hosts despite felids being the only definitive host. As cats play a major role in transmission to secondary mammalian hosts, the interaction between cats and these hosts should be a major factor determining final prevalence in the secondary host. This study investigates the prevalence of T. gondii in a natural population of Apodemus sylvaticus collected from an area with low cat density (<2·5 cats/km2). A surprisingly high prevalence of 40·78% (95% CI: 34·07%-47·79%) was observed despite this. A comparable level of prevalence was observed in a previously published study using the same approaches where a prevalence of 59% (95% CI: 50·13%-67·87%) was observed in a natural population of Mus domesticus from an area with high cat density (>500 cats/km2). Detection of infected foetuses from pregnant dams in both populations suggests that congenital transmission may enable persistence of infection in the absence of cats. The prevalences of the related parasite, Neospora caninum were found to be low in both populations (A. sylvaticus: 3·39% (95% CI: 0·12%-6·66%); M. domesticus: 3·08% (95% CI: 0·11%-6·05%)). These results suggest that cat density may have a lower than expected effect on final prevalence in these ecosystems.

Animal model of metastatic pheochromocytoma: evaluation by MRI and PET.

OBJECTIVE: The development of metastatic pheochromocytoma animal model provides a unique opportunity to study the physiology of these rare tumors and to evaluate experimental treatments. Here, we describe the use of small animal imaging techniques to detect, localize and characterize metastatic lesions in nude mice. METHODS: Small animal positron emission tomography (PET) imaging and magnetic resonance imaging (MRI) were used to detect metastatic lesions in nude mice following intravenous injection of mouse pheochromocytoma cells. [18F]-6-fluoro-dopamine ([18F]-DA) and [18F]-L-6-fluoro-3,4-dihydroxyphenylalanine, which are commonly used for localization of pheochromocytoma lesions in clinical practice, were selected as radiotracers to monitor metastatic lesions by PET. RESULTS: MRI was able to detect liver lesions as small as 0.5mm in diameter. Small animal PET imaging using [18F]-DA and [18F]-DOPA detected liver, adrenal gland, and ovarian lesions. CONCLUSION: We conclude that MRI is a valuable technique for tumor growth monitoring from very early to late stages of tumor progression and that animal PET confirmed localization of metastatic pheochromocytoma in liver with both radiotracers.

Evidence for high levels of vertical transmission in Toxoplasma gondii.

Toxoplasma gondii is a highly ubiquitous and prevalent parasite. Despite the cat being the only definitive host, it is found in almost all geographical areas and warm blooded animals. Three routes of transmission are recognised: ingestion of oocysts shed by the cat, carnivory and congenital transmission. In natural populations, it is difficult to establish the relative importance of these routes. This paper reviews recent work in our laboratory which suggests that congenital transmission may be much more important than previously thought. Using PCR detection of the parasite, studies in sheep show that congenital transmission may occur in as many as 66% of pregnancies. Furthermore, in families of sheep on the same farm, exposed to the same sources of oocysts, significant divergent prevalences of Toxoplasma infection and abortion are found between different families. The data suggest that breeding from infected ewes increases the risk of subsequent abortion and infection in lambs. Congenital transmission rates in a natural population of mice were found to be 75%. Interestingly, congenital transmission rates in humans were measured at 19.8%. The results presented in these studies differ from those of other published studies and suggest that vertical transmission may be much more important than previously thought.

Neospora caninum: detection in wild rabbits and investigation of co-infection with Toxoplasma gondii by PCR analysis.

Neospora caninum is an important pathogen of cattle causing significant economic loss. There is much current interest in wild animal reservoirs for this parasite. The role of the rabbit in this is currently unknown. DNA samples from the brains of wild rabbits (Oryctolagus cuniculus) collected from the Malham area of the Yorkshire dales were investigated by species-specific PCR for the presence of N. caninum and Toxoplasma gondii. We found prevalences of N. caninum of 10.5% (6/57) and T. gondii of 68.4% (39/57) with 8.8% (5/57) co-infected. Strain typing of T. gondii positive rabbits revealed strain types I-III were present in this population. Investigation of tissue distribution determined N. caninum DNA was most often detected in the brain and heart, less often in the tongue and not in the liver. To our knowledge this is the first report of N. caninum detection in naturally infected wild rabbits.

Evidence that primary infection of Charollais sheep with Toxoplasma gondii may not prevent foetal infection and abortion in subsequent lambings.

A study carried out on a sheep farm examined whether Toxoplasma gondii foetal infection and associated abortion occur in successive lambings. We identified 29 ewes that gave birth to lambs on at least 2 successive years over our study period, 2000-2003. Tissue samples from the progeny of these ewes were analysed by PCR to determine infection status with T. gondii. T. gondii-infected lambs were born in 31% of successive pregnancies. T. gondii-positive lambs were aborted in successive pregnancies in 21% of lambings during study period, 2000-2003. The frequency of successive abortions within this flock over the period 1992-2003 was 18%. If a lamb was congenitally infected there was a high risk (69%) that the successive lamb from that ewe would also be congenitally infected. Similarly, if a lamb was aborted there was a high risk (55%) of abortion in the next lamb produced. These data suggest that life-long immunity to T. gondii infections may not always be acquired following an initial infection and raises the question as to whether the mechanisms of T. gondii transmission prior to and during ovine pregnancies are fully understood.

Does vertical transmission contribute to the prevalence of toxoplasmosis?

Toxoplasma gondii is a ubiquitous parasite with a widespread distribution both in terms of geographical and host range. Although the definitive host is the cat, it is also a major health hazard to domestic animals and humans. Three routes of transmission are recognised (infection from the cat, carnivory and congenital transmission). We aimed to assess the relative importance of congenital transmission, using sheep as a model system, due to the lack of carnivory. We report, using PCR as a diagnostic tool, that congenital transmission occurs with high frequency (69%). If transmission from oocysts was important in sheep, we would expect sheep reared under the same environmental conditions (i.e. a single farm) to have a random distribution of Toxoplasma infection. Using breeding records in conjunction with PCR, some families were found to have high Toxoplasma prevalence and abortion while others were free of Toxoplasma infection and abortion (P < 0.01). This supports the notion that Toxoplasma may be transmitted vertically. In humans, we conducted a similar study and showed that Toxoplasma was transmitted from mother to baby in 19.8% of cases. Vertical transmission in Toxoplasma may be more important than previously thought and this knowledge should be considered in any eradication strategies.

Hepatic MR imaging with a dynamic contrast-enhanced isotropic volumetric interpolated breath-hold examination: feasibility, reproducibility, and technical quality.

PURPOSE: To evaluate the feasibility, reproducibility, and technical quality of a dynamic contrast material-enhanced isotropic three-dimensional (3D) volumetric interpolated breath-hold hepatic magnetic resonance (MR) imaging examination. MATERIALS AND METHODS: Fifty patients underwent 3D spoiled gradient-echo imaging (4.2/1.8 [repetition time msec/echo time msec]; flip angle, 12 degrees; interpolation in three directions; intermittent fat saturation; pixel size

MR hysterosalpingography: protocol development and refinement for simulating normal and abnormal fallopian tube patency--feasibility study with a phantom.

PURPOSE: To develop and refine a pulse sequence and protocol for testing the feasibility of magnetic resonance (MR) hysterosalpingography in a phantom model. MATERIALS AND METHODS: A phantom simulating the uterus, fallopian tubes, and surrounding pelvic cavity was constructed. T2-weighted acquisition strategies-breath-hold fast spin-echo, rapid acquisition with relaxation enhancement (RARE), and haff-Fourier RARE-were refined to acquire sequential 70-mm coronal imaging volumes. Contrast agent was injected into the introducing catheter entering the os of the simulated uterus. Interacquisition interval, type of contrast agent (eg, sterile saline solution or water), and quantity of contrast agent (eg, 1-5 mL per acquisition) were varied. Digital image subtraction was used to enhance image quality. Images were qualitatively analyzed and rated good, fair, or poor for temporal resolution, spatial resolution, fallopian tube conspicuity, and free spill conspicuity. Once the technique was refine, the phantom was reconfigured to simulate unilateral and bilateral hydrosalpinx. RESULTS: The RARE sequence with an 8-second interacquisition interval and a 5-mL interacquisition of sterile water produced good images of the simulated fallopian tubes and free spill. Depiction of unilateral and bilateral hydrosalpinx was also reliably demonstrated. CONCLUSION: This study with a phantom model demonstrates the feasibility of MR hysterosalpingography to depict normal and diseased fallopian tubes.

Abdominal MR imaging with a volumetric interpolated breath-hold examination.

PURPOSE: To compare a T1-weighted, three-dimensional (3D), gradient-echo (GRE) sequence for magnetic resonance (MR) imaging of the body (volumetric interpolated breath-hold examination, or VIBE) with a two-dimensional (2D) GRE breath-hold equivalent. MATERIALS AND METHODS: Twenty consecutive patients underwent 1.5-T MR imaging. The examinations included pre- and postcontrast (20 mL gadopentetate dimeglumine) fat-saturated 2D GRE breath-hold imaging and fat-saturated volumetric interpolated breath-hold imaging before, during (arterial phase), and after injection, with thin (2-mm source images) and thick (8-mm reconstruction images) sections. The three images were compared qualitatively and quantitatively (signal-to-noise ratio [SNR] and contrast-to-noise ratio [CNR]). RESULTS: Qualitatively, the 2-mm source images had poorer pancreatic edge definition on precontrast images compared with the other two data sets (P < .05). On gadolinium-enhanced images, scores for clarity of pancreatic edge, number of vessels visualized, and arterial ghosting were significantly lower for the postcontrast 2D GRE images. Quantitatively, SNR measurements in the liver, aorta, and renal cortex on pre- and postcontrast images were significantly higher for the 8-mm reconstruction images than for the 2D GRE or 2-mm source images (P < .05). Aorta-to-fat CNR was significantly higher on the 8-mm reconstruction images. CONCLUSION: Fat-saturated volumetric interpolated breath-hold images have quality comparable to that of conventional fat-saturated 2D GRE images.

T2-weighted MRI of the uterus: fast spin echo vs. breath-hold fast spin echo.

This study compared one routine T2-weighted fast spin echo (T2FSE) sequence with a breath-hold T2FSE (BH T2FSE) sequence of the female pelvis for image quality, uterine anatomy, lesion detection, and signal intensity measurements. Thirty-two consecutive women (mean age 41.7 years) were imaged at 1.5 T with one high-resolution routine T2FSE sequence and one BH T2FSE sequence in the sagittal plane as part of comprehensive pelvic magnetic resonance imaging. The different image sets were rated separately for imaging characteristics (overall image quality, uterine anatomy definition, lesion detection, and free fluid conspicuity) and then compared side by side. The image sets were also compared for artifacts (ghosting, blurring, pulsatility, and chemical shift misregistration). Signal-to-noise (S/N) and signal difference-to-noise (SD/N) ratios were calculated for the different uterine zones, uterine abnormalities, free fluid, rectus abdominis muscle, and bladder. Contrast-to-noise ratios (CNRs) were calculated for uterine abnormalities. Twenty-eight uterine abnormalities were detected in 20 patients and included leiomyomata (13 patients), adenomyosis (7 patients), benign endometrial polyps (6 patients), endometrial carcinoma (1 patient), and pregnancy (1 patient). BH T2FSE was superior or equivalent to T2FSE for overall image quality in 23/32 patients (71.8%), uterine anatomy definition in 19/32 patients (59.3%), and lesion detection in 13/20 patients (65%). BH T2FSE performed less well than T2FSE for free fluid conspicuity in 5/5 (100%) patients. BH T2FSE was equivalent to or less affected than T2FSE for ghosting artifact in 24/32 patients (75%) and blurring artifact in 29/32 patients (90.6%). Pulsatility and chemical shift artifacts were not problematic for either image set. S/N and SD/N were higher for all BH T2FSE determinations compared with T2FSE. For the endometrium, junctional zone, myometrium, and bladder, these differences were statistically significant. There were no statistically significant differences for CNR between the two image sets, although BH T2FSE values for leiomyomata, adenomyosis, and abnormal endometria were higher than those calculated for T2FSE. All pathology detected with T2FSE was detected on BH T2FSE despite the breath-hold sequence's inherently poorer spatial resolution compared with the non-breath-hold sequence. BH T2FSE may be able to replace T2FSE for some uterine applications with a substantial time savings.

HASTE MR imaging: description of technique and preliminary results in the abdomen.

HASTE (Half fourier Single-shot Turbo spin-Echo) is a single-section T2-weighted sequence that acquires images in less than 1 second. Images are breathing independent and possess a variety of other features useful for imaging the abdomen. The design of this technique is described. Clinical studies of 38 consecutive patients were performed using this technique. HASTE images were considered good in 28 and fair in 10 patients, including five patients who could not suspend respiration. Definition of liver and bowel was particularly clear.

Phase-modulated binomial RF pulses for fast spectrally-selective musculoskeletal imaging.

Two fat-suppressed three-dimensional gradient echo pulse sequences, FLASH and DESS (Double Echo in Steady-State), that have significantly reduced scan time compared with conventional chemical shift fat-suppression sequences are presented. This fat-suppression technique is based on selectively exciting water spins using a time-optimized binomial RF pulse pair at the water resonance frequency with a null in the excitation profile at the fat frequency. To minimize the total pulse length, the delay between the binomial components of the RF pulse is decreased from a standard jump-return implementation. To maintain the proper null frequency, the phase of the second RF pulse is shifted such that it returns the fat resonance back to its initial z position while further tipping the water spins. Nonselective phase-modulated RF pulse pairs can be implemented in 1.20 ms at 1.0 T, significantly reducing the minimum TR.

Water excitation MPRAGE MRI of VII and VIII cranial nerves.

OBJECTIVE: Our goal was to compare magnetization prepared rapid gradient echo--water excitation (MRPRAGE-WE) with conventional spin echo (CSE) in the evaluation of the VII and VIII cranial nerves. METHODS: One hundred three consecutive patients with symptoms referable to the VII/VIII nerves were studied with CSE T1 and MPRAGE-WE following intravenous gadolinium contrast agent. Each right and left nerve pair was independently evaluated for the presence of an enhancing mass and for visualization of the nerves. RESULTS: On the CSE images, 26 definite and 2 possible lesions were identified, whereas 28 definite and 2 possible abnormalities were seen on the MPRAGE-WE. Four cases were better identified on the MPRAGE-WE and one better seen on the CSE. This difference was not statistically significant (p = 0.19). CSE demonstrated the nerves partially in 23 instances and completely in 6; MPRAGE-WE showed the nerves partially in 35 and completely in 73. This was highly significant (p<0.001). CONCLUSION: With equivalent or slightly improved lesion detection and better visualization of the nerves, MPRAGE-WE may replace CSE in studying the VII/VIII nerves.

Optimization of a dual echo in the steady state (DESS) free-precession sequence for imaging cartilage.

Three-dimensional (3D) MR imaging of the knee is useful to detect cartilage abnormalities, although the tissue contrast in 3D gradient-recalled echo (GRE) sequences such as gradient-recalled acquisition in the steady state (GRASS) or fast low-angle shot (FLASH) is poor. T2 contrast can be added to a GRASS sequence by combining the signals from the first and second gradient echoes, which form immediately after and immediately before each radio frequency (RF) pulse in a 3D GRE sequence. We have optimized a 3D dual echo in the steady state (DESS) sequence, which produces one averaged image from the two echoes, for use in the detection of articular cartilage abnormalities. In the optimization process, we examined the imaging parameters of flip angle (alpha), repetition time (TR), echo time (TE), and bandwidth to maximize the contrast between cartilage and joint fluid. A theoretical simulation of the sequence was confirmed with experiments conducted on phantoms with known T1 and T2. On the basis of theoretical predictions and experiments using healthy volunteers, we determined that an optimized sequence with a bandwidth of 98 Hz per pixel, TR of 30 msec, a TE of 7.1 msec, and an alpha of 60 degrees produced the highest contrast between cartilage and fluid within a defined acquisition time of 6 minutes. Additional contrast was obtained by filtering the second-echo image to eliminate noise before adding it to the first-echo image.

Quantitation of the susceptibility difference between trabecular bone and bone marrow: experimental studies.

In this study we quantify the effects of different relaxation mechanisms on the signal intensity in gradient-echo images of tissue such as bone marrow in the presence of trabecular bone. The susceptibility difference between trabecular bone and soft tissue produces distortions in the magnetic lines of force which induce strong inhomogeneities in the static magnetic field. Diffusion of tissue protons in such magnetic field gradients produce a shortening of the transverse relaxation time T2, while the dephasing of the transverse magnetization due to susceptibility differences produces a shortening of the apparent relaxation time T2* as demonstrated in gradient-echo images. We have used specimens of dried human vertebrae with different bone densities immersed in either saline to simulate tissue water or an emulsion of oil and water to simulate bone marrow to quantify these relaxation mechanisms in vitro. We have measured the MR relaxation times T1, T2, and T2* of protons within the trabecular spaces and correlated their variations with trabecular bone density. We have found that in vitro, at 1.5 T, the relaxation times T1 and T2 do not show significant variations with bone density and there are no significant contributions to the transverse relaxation rate due to the diffusion of tissue water in the magnetic field gradients. However, the relaxation rate, 1/T2*, of saline in the presence of trabecular bone increases at a rate of 0.2 s-1/mg/cc due to the dephasing of the transverse magnetization in the magnetic field inhomogeneities. Similar bone density-related T2* variations were observed for fat protons within the trabeculae where the chemical-shift-induced modulations of signal intensity in an oil-water emulsion have been separated from the susceptibility-induced relaxation effects. In addition, we have verified these effects in vivo and quantified in vivo variations in fat and water relaxation rates of bone marrow in the epiphysis and diaphysis in the appendicular skeleton of normal volunteers and found that both fat and water T2* are shorter in the epiphysis compared to the diaphysis, which correlates well with previous observations.

Improved detectability in low signal-to-noise ratio magnetic resonance images by means of a phase-corrected real reconstruction.

We show that for magnetic resonance (MR) images with signal-to-noise ratio (SNR) less than 2 it is advantageous to use a phase-corrected real reconstruction, rather than the more usual magnitude reconstruction. We discuss the results of the phase correction algorithm used to experimentally verify the result. We supplement the existing literature by presenting closed form expressions (in an MR context) for the probability distribution and first moments of the signal resulting from a magnitude reconstruction.

Regional T2 and sodium concentration estimates in the normal human brain by sodium-23 MR imaging at 1.5 T.

We have analyzed multiple spin echo Na magnetic resonance (MR) images of the normal human brain in four volunteer subjects. Utilizing the much slower T2 decay of the CSF, we obtained images that separate cortex from the surrounding CSF and measured regional T2 of cortex, white matter, CSF, vitreous humor, and superior sagittal sinus. Assuming a sodium concentration of 145 mM in the vitreous humor, we normalized the extrapolated equilibrium magnetization (M0) for each region to the M0 of the vitreous humor to estimate regional sodium concentration. We found that regional T2 measurements more consistently distinguish the high signal regions of cortex, CSF, and blood than do our regional sodium estimates, whereas regional sodium estimates adequately distinguish white matter from cortex. The T2 values of white matter and cortex, on the other hand, are nearly identical. Our work addresses the problems encountered in establishing norms for clinical application of Na MR and represents a step toward establishing those norms.

Multiple short-echo (2.5-ms) quantitation of in vivo sodium T2 relaxation.

The MR behavior of the sodium-23 nucleus in vivo is a complex problem which has generated considerable interest over the last 20 years. Early studies on excised tissue samples revealed that the sodium nucleus exhibited a two-component T2 relaxation. This biexponential T2 relaxation was characterized by a short component with a T2 = 0.7-4.8 ms, and a long component with a T2 = 7.0-26.0 ms. We have developed a 3D pulse sequence capable of performing multiple Hahn echo in vivo sodium-23 imaging at echo times as short as 2.5 ms. This sequence obtains the shorter spin echo times by presaturating the spins outside of the desired imaging region, allowing the use of nonselective rf pulses. Using this sequence we have been able to quantify the long and short T2 components of normal brain tissue, vitreous humor of the eye, and a rabbit VX-2 carcinoma. We found that gray matter and white matter of normal brain have a monoexponential T2 relaxation with T2 = 17.6 +/- 2.4 ms. The vitreous humor T2 relaxation is also monoexponential with T2 = 56.8 +/- 2.1 ms. However, we find that some of the rabbit VX2 carcinomas exhibit a biexponential T2 decay with a short component of 3.3 +/- 4.6 ms and a long component of 22.0 +/- 9.0 ms.