Magnetization Transfer Signal Research Articles

The effect of aquaporin-4 inhibition on cerebrospinal fluid-tissue water exchange in mouse brain detected by magnetization transfer indirect spin labeling MRI.

The fluid transport of cerebrospinal fluid (CSF) and interstitial fluid in surrounding tissues plays an important role in the drainage pathway that facilitates waste clearance from the brain. This pathway is known as the glymphatic or perivascular system, and its functions are dependent on aquaporin-4 (AQP4). Recently, magnetization transfer indirect spin labeling (MISL) magnetic resonance imaging (MRI) has been proposed as a noninvasive and noncontrast-enhanced method for detecting water exchange between CSF and brain tissue. In this study, we first optimized the MISL sequence at preclinical 3 T MRI, and then studied the correlation of MISL in CSF with magnetization transfer (MT) in brain tissue, as well as the altered water exchange under AQP4 inhibition, using C57BL/6 mice. Results showed a strong correlation of MISL signal with MT signal. With the AQP4 inhibitor, we observed a significant decrease in MISL value (P < 0.05), suggesting that the hampered AQP4 activity led to decreased water exchange between CSF and brain tissue or the impairment of the glymphatic function. Overall, our findings demonstrate the potential application of MISL in assessing brain water exchange at 3 T MRI and its potential clinical translation.

CEST2022 - mapping multi-pool CEST signal changes in an animal model of brain tumor with quasi-steady-state reconstruction-empowered CEST quantification

Chemical exchange saturated transfer (CEST) MRI has biomarker potential to assess tissue microenvironment in brain tumors. Multi-pool Lorentzian or spinlock models provides useful insights into the CEST contrast mechanism. However, T1 contribution to the complex overlapping effects of brain tumors is difficult under the non-equilibrium state. Therefore, this study evaluated T1 contributions on multi-pool parameters with quasi-steady-state (QUASS) algorithm reconstructed equilibrium data. MRI scans were performed in rat brain tumor models, including relaxation, diffusion, and CEST imaging. A pixel-wise seven-pool spinlock-model was employed to fit QUASS reconstructed CEST Z-spectra and evaluated the magnetization transfer (MT), amide, amine, guanidyl, and nuclear-overhauled effect (NOE) signals in tumor and normal tissues. In addition, T1 was estimated from the spinlock-model fitting and compared with measured T1. We observed tumor had a statistically significant increase in the amide signal (p < 0.001) and decreases in the MT and NOE signals (p < 0.001). On the other hand, the differences in amine and guanidyl between the tumor and contralateral normal regions were not statistically significant. The differences between measured and estimated T1 values were 8% in the normal tissue and 4% in the tumor. Furthermore, the isolated MT signal strongly correlated with R1 (r = 0.96, P < 0.001). In summary, we successfully unraveled multi-factorial effects in the CEST signal using spinlock-model fitting and QUASS method and demonstrated the effect of T1 relaxation on MT and NOE.

MRI detection of brain gadolinium retention in multiple sclerosis: Magnetization transfer vs. T1-weighted imaging.

Evidence of brain gadolinium retention has affected gadolinium-based contrast agent usage. It is, however, unclear to what extent macrocyclic agents are retained and whether their in vivo detection may necessitate nonconventional MRI. Magnetization transfer (MT) could prove suitable to detect gadolinium-related signal changes since dechelated gadolinium ions bind to macromolecules. Therefore, this study aimed to investigate associations of prior gadolinium administrations with MT and T1 signal abnormalities. A cohort of 23 persons with multiple sclerosis (MS) (18 females, 5 males, 57±8.0years) with multiple past gadolinium administrations (median 6, range 3-12) and 23 age- and sex-matched healthy controls underwent 1.5 Tesla MRI with MT, T1-weighted 2-dimensional spin echo, and T1-weighted 3-dimensional gradient echo. The signal intensity index was assessed by MRI in gadolinium retention predilection sites. There were dose-dependent associations of the globus pallidus signal on gradient echo (r=.55, p<.001) and spin echo (r=.38, p=.013) T1-weighted imaging, but not on MT. Relative to controls, MS patients had higher signal intensity index in the dentate nucleus on T1-weighted gradient echo (1.037±0.040 vs. 1.016±0.023, p=.04) with a similar trend in the globus pallidus on T1-weighted spin echo (1.091±0.034 vs. 1.076±0.014, p=.06). MT detected no group differences. Conventional T1-weighted imaging provided dose-dependent associations with gadolinium administrations in MS, while these could not be detected with 2-dimensional MT. Future studies could explore newer MT techniques like 3D and inhomogenous MT. Notably, these associations were identified with conventional MRI even though most patients had not received gadolinium administrations in the preceding 9years, suggestive of long-term retention.

Inhomogeneous magnetization transfer imaging: Concepts and directions for further development.

Off-resonance radio frequency irradiation can induce the ordering of proton spins in the dipolar fields of their neighbors, in molecules with restricted mobility. This dipolar order decays with a characteristic relaxation time, T1D , that is very different from the T1 and T2 relaxation of the nuclear alignment with the main magnetic field. Inhomogeneous magnetization transfer (ihMT) imaging is a refinement of magnetization transfer (MT) imaging that isolates the MT signal dependence on dipolar order relaxation times within motion-constrained molecules. Because T1D relaxation is a unique contrast mechanism, ihMT may enable improved characterization of tissue. Initial work has stressed the high correlation between ihMT signal and myelin density. Dipolar order relaxation appears to be much longer in membrane lipids than other molecules. Recent work has shown, however, that ihMT acquisitions may also be adjusted to emphasize different ranges of T1D . These newer approaches may be sensitive to other microstructural components of tissue. Here, we review the concepts and history of ihMT and outline the requirements for further development to realize its full potential.

Average saturation efficiency filter (ASEF) for CEST imaging.

Endogenous CEST signal usually has low specificity due to contamination from the magnetization transfer effect and from fast exchanging labile protons with close Larmor frequencies. We propose to improve CEST signal specificity with an average saturation efficiency filter (ASEF). ASEF measures the difference between CEST signals acquired with similar average irradiation power but largely different duty cycles (DC), for example, a continuous wave or a high DC pulse train versus a low DC one. Simulation and Cr phantom studies were performed to evaluate the characteristics of ASEF for CEST. Theoretical and simulation studies show that ASEF can suppress fast exchanging processes, with only a small loss of chemical exchange contrast for slow-to-intermediate exchange rates if the difference in DC is large. In the RF offset range of 2 to 5 ppm with an averaged saturation power of 0.8 and 1.6 microteslas, there is a mismatch of ∼0.1% to 2% in the magnetization transfer signal between saturation by continuous wave and a pulse train with DC=15% and pulse duration of 24 ms, respectively. This mismatch can be minimized by careful selection of saturation power, pulse duration, and DC differences or by applying a small fudge factor between the 2 irradiation powers. Phantom studies of Cr confirmed that ASEF can minimize the magnetization transfer effect and reduce sensitivity to fast exchange processes. ASEF can improve the specificity of slow-to-intermediate exchanging CEST signal with a relatively small loss of sensitivity.

Quantitative Magnetization Transfer Detects Renal Fibrosis in Murine Kidneys With Renal Artery Stenosis.

Renal fibrosis is a common pathway in tubulointerstitial injury and a major determinant of renal insufficiency. Collagen deposition, a key feature of renal fibrosis, may serve as an imaging biomarker to differentiate scarred from healthy kidneys. To test the feasibility of using quantitative magnetization transfer (qMT), which assesses tissue macromolecule content, to measure renal fibrosis. Prospective. Fifteen 129S1 mice were studied 4 weeks after either sham (n = 7) or unilateral renal artery stenosis (RAS, n = 8) surgeries. Magnetization transfer (MT)-weighted images were acquired at 16.4T using an MT-prepared fast-low-angle-shot sequence. Renal B0, B1, and T1 maps were also acquired, using a dual-echo gradient echo, an actual flip angle, and inversion recovery method, respectively. A two-pool model was used to estimate the bound water fraction (f) and other tissue imaging biomarkers. Masson's trichrome staining was subsequently performed ex vivo to evaluate renal fibrosis. Comparisons of renal parameters between sham and RAS were performed using independent samples t-tests. Pearson's correlation was conducted to investigate the relationship between renal fibrosis by histology and the qMT-derived bound pool fraction f. The two-pool model provided accurate fittings of measured MT signal. The qMT-derived f of RAS kidneys was significantly increased compared to sham in all kidney zones (renal cortex [CO], 7.6 ± 2.4% vs. 4.6 ± 0.6%; outer medulla [OM], 8.2 ± 4.2% vs. 4.2 ± 0.9%; inner medulla [IM] + P, 5.8 ± 1.6% vs. 2.9 ± 0.6%, all P < 0.05). Measured f correlated well with histological fibrosis in all kidney zones (CO, Pearson's correlation coefficient r = 0.95; OM, r = 0.93; IM + P, r = 0.94, all P < 0.05). The bound pool fraction f can be quantified using qMT at 16.4T in murine kidneys, increases significantly in fibrotic RAS kidneys, and correlates well with fibrosis by histology. Therefore, qMT may constitute a valuable tool for measuring renal fibrosis in RAS. 1 TECHNICAL EFFICACY STAGE: 3.

Background suppressed magnetization transfer MRI.

Up to 30% of the hydrogen atoms in brain tissue are part of molecules ("semisolids") other than water. In MRI, their magnetization is typically not observed directly, but can influence the water magnetization through magnetization transfer (MT). Comparison of MRI scans differentially sensitized to MT allows estimation of the semisolid fraction and potential changes with disease. Here, we present an approach designed to improve this estimate by measuring the size of the MT effect in a single scan. A stimulated echo sequence was used to generate a spatial pattern in the longitudinal water magnetization, which was then given time to exchange with semisolids. After saturating the remaining water magnetization, reverse exchange was allowed to partly re-establish the original water magnetization pattern. The third excitation pulse then formed a stimulated echo out of this pattern. MT data were obtained on 10 human subjects at 7 T with varying exchange times. The images showed the expected time dependence of signal associated with the forward and reverse exchange processes. Excellent suppression of non-exchanging background signal was achieved. As expected, this suppression came at the price of a substantial reduction in exchange-related signal (by ~75% compared to the signal in saturation recovery MT), in part because of the reliance on a 2-step exchange process. The results demonstrate an MT signal can be observed in a single acquisition without subtraction. This may be advantageous for MT measurements when signal instabilities related to motion and physiological variations exceed thermal noise sources.

Ultrahigh field imaging of myelin disease models: Toward specific markers of myelin integrity?

Specific magnetic resonance imaging (MRI) markers of myelin are critical for the evaluation and development of regenerative therapies for demyelinating diseases. Several MRI methods have been developed for myelin imaging, based either on acquisition schemes or on mathematical modeling of the signal. They generally showed good sensitivity but validation for specificity toward myelin is still warranted to allow a reliable interpretation in an in vivo complex pathological environment. Experimental models of dys-/demyelination are characterized by various levels of myelin disorders, axonal damage, gliosis and inflammation, and offer the opportunity for powerful correlative studies between imaging metrics and histology. Here, we review how ultrahigh field MRI markers have been correlated with histology in these models and provide insights into the trends for future developments of MRI tools in human myelin diseases. To this end, we present the biophysical basis of the main MRI methods for myelin imaging based on T1 , T2 , water diffusion, and magnetization transfer signal, the characteristics of animal models used and the outcomes of histological validations. To date such studies are limited, and demonstrate partial correlations with immunohistochemical and electron microscopy measures of myelin. These MRI metrics also often correlate with axons, glial, or inflammatory cells in models where axonal degeneration or inflammation occur as potential confounding factors. Therefore, the MRI markers' specificity for myelin is still perfectible and future developments should improve mathematical modeling of the MR signal based on more complex systems or provide multimodal approaches to better disentangle the biological processes underlying the MRI metrics.

A pH-Responsive MRI Agent that Can Be Activated Beyond the Tissue Magnetization Transfer Window.

A terbium-based complex that displays a water exchange CEST resonance well outside the normal magnetization transfer (MT) frequency range of tissues provides a direct readout of pH values by MRI. Deprotonation of the phenolic proton in this complex results in a frequency shift of 56 ppm in a bound water molecule exchange peak between pH 5 and 8. This allows direct imaging of pH without prior knowledge of the agent concentration and with essentially no interference from the tissue MT signal.

A pH‐Responsive MRI Agent that Can Be Activated Beyond the Tissue Magnetization Transfer Window

AbstractA terbium‐based complex that displays a water exchange CEST resonance well outside the normal magnetization transfer (MT) frequency range of tissues provides a direct readout of pH values by MRI. Deprotonation of the phenolic proton in this complex results in a frequency shift of 56 ppm in a bound water molecule exchange peak between pH 5 and 8. This allows direct imaging of pH without prior knowledge of the agent concentration and with essentially no interference from the tissue MT signal.

Relaxation-compensated CEST-MRI of the human brain at 7 T: Unbiased insight into NOE and amide signal changes in human glioblastoma

Endogenous chemical exchange saturation transfer (CEST) effects of protons resonating near to water protons are always diluted by competing effects such as direct water saturation and semi-solid magnetization transfer (MT). This leads to unwanted T2 and MT signal contributions that contaminate the observed CEST signal. Furthermore, all CEST effects appear to be scaled by the T1 relaxation time of the mediating water pool. As MT, T1 and T2 are also altered in tumor regions, a recently published correction algorithm yielding the apparent exchange-dependent relaxation AREX, is used to evaluate in vivo CEST effects. This study focuses on CEST effects of amides (3.5ppm) and Nuclear-Overhauser-mediated saturation transfer (NOE, −3.5ppm) that can be properly isolated at 7T. These were obtained in 10 glioblastoma patients, and this is the first comprehensive study where AREX is applied in human brain as well as in human glioblastoma. The correction of CEST effects alters the contrast significantly: after correction, the CEST effect of amides does not show significant contrast between contrast enhancing tumor regions and normal tissue, whereas NOE drops significantly in the tumor area. In addition, new features in the AREX contrasts are visible. This suggests that previous CEST approaches might not have shown pure CEST effects, but rather water relaxation shine-through effects. Our insights help to improve understanding of the CEST effect changes in tumors and correlations on a cellular and molecular level.

Improving the accuracy of cross‐relaxation imaging

AbstractCross‐relaxation imaging (CRI) provides biomarkers sensitive to the macromolecular content of tissue. Although the CRI parameters are sufficiently precise to exhibit significant correlations with macromolecular content in tissue, their accuracy is hindered by the CRI modeling and measurement variability. In this article, several sources of CRI variability are examined, such as T1 mapping bias, magnetization transfer signal drift, and inaccuracies due to tissue modeling. Simple corrections schemes are proposed to account for these effects and to improve the CRI accuracy. © 2012 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 22, 67–72, 2012

Z-spectroscopy with Alternating-Phase Irradiation

Magnetization transfer (MT) MRI and Z-spectroscopy are tools to study both water–macromolecule interactions and pH-sensitive exchange dynamics between water and the protons of mobile chemical groups within these macromolecules. Both rely on saturation of frequencies offset from water and observation of the on-resonance water signal. In this work, an RF saturation method called Z-spectroscopy with Alternating-Phase Irradiation (ZAPI) is introduced. Based on the T 2-selectivity of the irradiation pulse, ZAPI can be used to separate the different contributions to a Z-spectrum, as well as to study the T 2 distribution of the macromolecules contributing to the MT signal. ZAPI can be run at resonance for water and with low power, thus minimizing problems with specific absorption rate (SAR) limits in clinical applications. In this paper, physical and practical aspects of ZAPI are discussed and the sequence is applied in vitro to sample systems and in vivo to rat head to demonstrate the method.

Systematic Variation of Off-Resonance Prepulses for Clinical Magnetization Transfer Contrast Imaging at 0.2, 1.5, and 3.0 Tesla

The aim of the presented study was to evaluate pulsed magnetization transfer contrast (MTC) effects using saturation pulses of variable off-resonance frequency and radio frequency (RF) amplitude for a variety of tissue types (white and gray matter, liver, kidney, spleen, muscle, and articular cartilage) in human subjects at field strengths of 0.2, 1.5, and 3.0 Tesla. MTC imaging studies of the head, knee, and abdomen were performed using an adapted multiple MTC (mMTC) module in 3 healthy volunteers for all field strengths. This mMTC pulse module applies a variable Gaussian shaped magnetization transfer (MT) saturation pulse in a proton-density weighted RF-spoiled gradient echo sequence. It allows for both a flexible MT pulse design and performance of consecutive measurements with variation of amplitude and off-resonance frequency, whereas keeping other MT pulse parameters unchanged. Magnetization transfer signal ratio (MTR) maps were calculated on a pixel-by-pixel basis. Additional mMTC imaging measurements were performed using an agar-water phantom. For assessment of undesired direct saturation effects of the MT pulse on the water pool, numerical simulations based on Bloch's equations were performed and analyzed. The results indicate that MTR values for given MT pulses (pulse shape, off-resonance frequency and flip angle) are larger at higher magnetic field strengths. For white matter, gray matter, cartilage, and muscle, an increase of 10% to 30% was found at 3.0 T when compared with 1.5 T. Low magnetic field strength of 0.2 T led to MTR values of one third to half the values at 1.5 T. MTR values for abdominal tissues were partly lower at 3.0 T compared with 1.5 T, which might be related to reduced B1 field strengths at 3.0 T due to dielectric effects. The increased MT effect at a higher field strength can partly compensate the specific absorption rate related problems in MTC applications. It is shown that for flip angles of 700 degrees to 900 degrees and offset frequencies of 1000 Hz to 1500 Hz, high quality MTR maps could be obtained at an acceptable level of direct saturation for all field strengths. Furthermore, if the better signal-to-noise ratio at higher magnetic fields is taken into account, quality of MTR maps of the head and the knee at 3.0 T was clearly improved compared with lower fields under optimized and comparable conditions.

Magnetization transfer MRI for quantitative assessment of intestinal fibrosis in Crohnʼs disease

To develop a non-invasive method for detecting and quantifying intestinal fibrosis in patients with Crohn's disease using magnetization transfer (MT) magnetic resonance imaging (MRI). MT-MRI is more specific than traditional MRI for detecting tissue fibrosis by differentiating between free tissue water and water closely associated with macromolecules such as collagen. We hypothesize that changes in the MT signal profile can be used to differentiate and quantitatively characterize intestinal fibrosis, and will be more sensitive and specific for fibrosis than traditional MRIT1 and T2 relaxation times. Intestinal fibrosis was experimentally induced in Lewis strain rats. During laparotomy peptidoglycan-polysaccharide (PG-PS) was injected subserosally into the intestinal wall of the cecum, ileum, and distal Peyer's patches of four rats. Five control animals were similarly injected with human serum albumin (HSA). The PG-PS injected animals developed chronic intestinal inflammation, granulomas, and intense fibrosis 21 days after injection. Ex vivo intestinal tissue samples were scanned in a Varian Inova 2.0 T, 31 cm clear bore system equipped with Acustar S-180 actively shielded gradients and an MR probe. For magnetization transfer, a series of RF pulses were applied from -100 Hz to + 100 kHz off-resonance at three different RF power levels. In vivo MT-MRI images of a whole rat abdomen were also obtained. After undergoing MT-MRI scanning, intestinal histopathology determined the extent of tissue fibrosis. The standard MR imaging parameters, T1 and T2 relaxation times, as well as the MT data were recorded for both PG-PS and HSA samples. There was no difference between the T1 and T2 relaxation times. The MT data were analyzed and reduced into factors indicating the percent solid matter and overall tissue rigidity. The MT ratio (MTR) = 100*(1 -Msat/Mo) where Msat represents MT signal at 10 kHz off-resonance, and Mo represents MT signal at 100 kHz off-resonance. The mean MTR from PG-PS rats was 46.27 (SD 4.14), and control rats was 38.07 (SD 4.76). This demonstrated a statistically significant difference (p = 0.03) between fibrotic and non-fibrotic tissue. Histopathology confirmed the presence of fibrosis in the PG-PS rats, and lack of fibrosis in the control rats. (1) As expected, the data demonstrate that standard T1 and T2 relaxation times were not appreciably different. This confirms that traditional MRI is not sufficiently sensitive to detect intestinal fibrosis. (2) The MT data collected from rats with experimental Crohn's were statistically significantly different than control rats without fibrosis. This supports our hypothesis that MT-MRI can be used to distinguish intestinal fibrosis from non-fibrotic tissue. Furthermore, the MT profile provides a quantification of tissue fibrosis which will allow the clinician to follow disease progression. This technique has the significant advantage over currently available imaging modalities without exposing the subject to ionizing radiation.

Continuous arterial spin labeling using a train of adiabatic inversion pulses

To develop a simple and robust magnetic resonance imaging (MRI) pulse sequence for the quantitative measurement of blood flow in the brain and cerebral tumors that has practical implementation advantages over currently used continuous arterial spin labeling (CASL) schemes. Presented here is a single-coil protocol that uses a train of hyperbolic secant inversion pulses to produce continuous arterial spin inversion for perfusion weighting of fast spin echo images. Flow maps of normal rat brains and those containing a 9L gliosarcoma orthotopic tumor model conditions were acquired with and without carbogen. The perfusion-weighted images have reduced magnetization transfer signal degradation as compared to the traditional single-coil CASL while avoiding the use of a more complex two-coil CASL technique. Blood flow measurements in tumor and normal brain tissue were consistent with those previously reported by other CASL techniques. Contralateral and normal brain showed increased blood flow with carbogen breathing, while tumor tissue lacked the same CO(2) reactivity. This variation of the CASL technique is a quantitative, robust, and practical single-coil method for measuring blood flow. This CASL method does not require specialized radiofrequency coils or amplifiers that are not routinely used for anatomic imaging of the brain, therefore allowing these flow measurements to be easily incorporated into traditional rodent neuroimaging protocols.

Changes in Magnetization Transfer MRI Correlate with Spreading Depression–Induced Astroglial Reactivity and Increased Protein Expression in Mice

Gliosis refers to a range of glial cell transformations that vary according to specific brain pathologic states. Disease, however, is not a prerequisite for gliosis because glial reactivity may also be seen in regions of increased physiologic activity. Our study tests the hypothesis that high-field-strength magnetization transfer MRI is a sensitive technique for detecting transient glial reactivity after experimental spreading depression, a relatively benign perturbation unaccompanied by cell injury. Unilateral neocortical spreading depression was elicited in mouse cerebral hemispheres and confirmed by transcranial blood flow and extracellular potential measurements. After 3 days, mice were imaged at 4 T using magnetization transfer techniques. Astroglial reactivity was determined immunohistochemically, and protein expression in control and experimental hemispheres was compared using proteomic techniques. Sixteen ([mean +/- SD] +/- 3) spreading depressions (n = 10) were recorded in experimental hemispheres. Spreading depression was never observed in control hemispheres. At 3 days, an 8% decrease (p < 0.05, n = 4) in magnetization transfer signal intensity was measured in experimental hemispheres, which was associated with a 37% increase (p < 0.001, n = 4) in the intensity of glial fibrillary acidic protein staining. Proteomic analysis performed 3 days after the induction of spreading depression showed upregulation of at least 56 proteins, including extracellular and intracellular elements. Magnetization transfer at 4.0-T MRI is a sensitive method for detecting glial reactivity and changes in protein expression not associated with cell injury. These results suggest magnetization transfer MRI techniques may have potential for detecting glial reactivity in physiologic processes such as learning and in early disease states.

Quantitative and qualitative assessment of articular cartilage in the goat knee with magnetization transfer imaging

We investigated the role of collagen in the magnetization transfer (MT) effect in contrast to other macromolecules. By means of phantoms made of collagen, chondroitin sulfate (CS) and albumin, MR parameters have been optimized in order to reduce the acquisition time and improve the sensitivity, as well as to minimize the contributions from CS and albumin to the MT induced signal attenuation. The same method was used to study cartilage ex vivo (bovine articular and nasal cartilage plugs) and in vivo (goat knee femoral chondyle). In phantom samples, the MT signal attenuation depended on the collagen concentration while contributions from the other macromolecules were found to be minimal. In average, analysis of MT images revealed a ∼25%, ∼35% and ∼30% signal attenuation in 10% w/v type I collagen gels, cartilage plugs, and cartilage from the weight-bearing areas of the goat knee, respectively. Biochemical data revealed that treatment of cartilage plugs with bacterial collagenase led to collagen depletion and correspondingly to a decrease of the MT response. In contrast, trypsin-induced proteoglycan loss in cartilage plugs did not alter the MT effect. A significant correlation was observed between the collagen content in these plugs and their respective MT ratios and the rate constant k for the exchange process bound versus free water. Finally, data obtained from in vivo MT measurement of the goat knee demonstrated that intra-articular injection of papain might not only cause degradation of proteoglycans but also a change in collagen integrity in a dose-dependent manner. We conclude that in vivo measurement of MT ratios gives quantitative and qualitative information on the collagen status and may be applied for the routine evaluation of normal and abnormal articular cartilage.

Magnetization transfer of fluoxetine in the human brain using fluorine magnetic resonance spectroscopy

Fluorine magnetic resonance spectroscopy ( 19F MRS) measurements of fluoxetine and metabolite concentration in the human brain underestimate true drug levels because of a bound, MRS-“invisible” pool of drug molecules. Magnetization transfer (MT) spectroscopy may be a useful technique for characterizing this bound pool of fluoxetine in the brain. Six subjects on consistent daily doses of fluoxetine underwent 19F MT spectroscopy on a 1.5-T scanner using a train of three preparation pulses at −3000 Hz off resonance with 0.5 W of peak power deposition in tissue. One subject was scanned at multiple time points after initiation of drug therapy. Magnetization transfer signal contrast was quantified using VARPRO-based time domain fitting software. Magnetization transfer signal contrast was quantifiable with mean MT signal depression of 12.5% (SD = 5.0, n = 6). An inverse relationship between brain concentration and the MT signal contrast of fluoxetine was found ( r = −.82, Spearman coefficient = .007). This study is the first in vivo application of 19F MT spectroscopy and the first to demonstrate a quantifiable MT effect for a psychotropic medication in the human brain. Findings suggest that fluoxetine is substantially bound in the brain and that individual differences, inversely related to brain concentration, can be detected in the magnitude of MT contrast.

Quantitative magnetic resonance imaging in the assessment of degenerative disc disease.

Understanding degenerative intervertebral disc diseases hinges on the ability to objectively and noninvasively assess the disc matrix composition and integrity. The potential of quantitative magnetic resonance imaging to meet these demands was evaluated. Analyzing the T1 and T2 signal patterns in the nucleus pulposus with increasing Thompson morphological grade revealed a significant reduction related to grade. This significant decrease in T1 and T2 in the nucleus pulposus with grade 4 degeneration and the corresponding low correlation coefficients with respect to the content of individual matrix molecules suggest that matrix integrity plays an important and distinct role in determining T1 and T2 signal. Similarly, the significant increase in magnetization transfer in the nucleus pulposus observed in grade 4 degeneration did not correlate with the changes in molecular content in these highly degenerated discs. Again, this lack of correlation clearly indicates that the tissue integrity and matrix composition independently contribute to the magnetization transfer signal. This study presents the first clear evidence that quantitative magnetic resonance analysis reflects not only the disc matrix composition, but also the structural integrity of the matrix of the disc.