Shalom Michaeli

Proton T2 relaxation study of water, N-acetylaspartate, and creatine in human brain using Hahn and Carr-Purcell spin echoes at 4T and 7T.

Carr‐Purcell and Hahn spin‐echo (SE) measurements were used to estimate the apparent transverse relaxation time constant (T  †2 ) of water and metabolites in human brain at 4T and 7T. A significant reduction in the T  †2 values of proton resonances (water, N‐acetylaspartate, and creatine/phosphocreatine) was observed with increasing magnetic field strength and was attributed mainly to increased dynamic dephasing due to increased local susceptibility gradients. At high field, signal loss resulting from T  †2 decay can be substantially reduced using a Carr‐Purcell‐type SE sequence. Magn Reson Med 47:629–633, 2002.

Different excitation and reception distributions with a single‐loop transmit‐receive surface coil near a head‐sized spherical phantom at 300 MHz

Calculations and experiments were used to examine the B1 field behavior and signal intensity distribution in a 16‐cm diameter spherical phantom excited by a 10‐cm diameter surface coil at 300 MHz. In this simple system at this high frequency very complex RF field behavior exists, resulting in different excitation and reception distributions. Included in this work is a straightforward demonstration that coil receptivity is proportional to the magnitude of the circularly polarized component of the B1 field that rotates in the direction opposite to that of nuclear precession. It is clearly apparent that even in very simple systems in head‐sized samples at this frequency it is important to consider the separate excitation and reception distributions in order to understand the signal intensity distribution. Magn Reson Med 47:1026–1028, 2002.

Assessment of brain iron and neuronal integrity in patients with Parkinson's disease using novel MRI contrasts

Postmortem demonstration of increased iron in the substantia nigra (SN) is a well‐appreciated finding in Parkinsons disease (PD). Iron facilitates generation of free radicals, which are thought to play a role in dopamine neuronal loss. To date, however, magnetic resonance imaging (MRI) has failed to show significant in vivo differences in SN iron levels in subjects with PD versus control subjects. This finding may be due to the limitations in tissue contrasts achievable with conventional T1‐ and T2‐weighted MRI sequences that have been used. With the recent development of novel rotating frame transverse (T2ρ) and longitudinal (T1ρ) relaxation MRI methods that appear to be sensitive to iron and neuronal loss, respectively, we embarked on a study of 8 individuals with PD (Hoehn & Yahr, Stage II) and 8 age‐matched control subjects. Using these techniques with a 4T MRI magnet, we assessed iron deposits and neuronal integrity in the SN. First, T2ρ MRI, which is reflective of iron‐related dynamic dephasing mechanisms (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities), demonstrated a statistically significant difference between the PD and control group, while routine T2 MRI did not. Second, T1ρ measurements, which appear to reflect upon neuronal count, indicated neuronal loss in the SN in PD. We show here that sub‐millimeter resolution T1ρ and T2ρ MRI relaxation methods can provide a noninvasive measure of iron content as well as evidence of neuronal loss in the midbrain of patients with PD.

In vivo 1H2O T †2 measurement in the human occipital lobe at 4T and 7T by Carr‐Purcell MRI: Detection of microscopic susceptibility contrast

A high‐resolution spin‐echo imaging method is presented (called CP‐LASER) which exploits the spin refocusing capability of an adiabatic Carr‐Purcell (CP) pulse sequence to measure apparent 1H2O transverse relaxation (T  †2 ) and generate contrast based on microscopic tissue susceptibility. High‐resolution CP‐LASER images of the human occipital lobe were acquired at four different echo times from six subjects at 4T and eight subjects at 7T to investigate the effect of magnetic field strength (B0) and the CP interpulse time (τcp) on T  †2 . Susceptibility contrast was identified and T  †2 was quantified for long τcp (>10 ms) and short τcp (7 ms at 4T and 6 ms at 7T) in gray matter, white matter, and cerebral spinal fluid. The 1H2O relaxation rate constants (1/T  †2 ) of gray and white matter each increased approximately linearly with field strength and T  †2 was inversely related to τcp. The average T  †2 value of gray matter was 19% and 9% smaller than that of white matter at 4T and 7T, respectively. These results are consistent with higher levels of compartmentalized ferritin and increased blood volume in gray matter compared to white matter in this region of the brain. Magn Reson Med 47:742–750, 2002.

Exchange-influenced T2ρ contrast in human brain images measured with adiabatic radio frequency pulses

Transverse relaxation in the rotating frame (T2ρ) is the dominant relaxation mechanism during an adiabatic Carr–Purcell (CP) spin‐echo pulse sequence when no delays are used between pulses in the CP train. The exchange‐induced and dipolar interaction contributions (T2ρ,ex and T2ρ,dd) depend on the modulation functions of the adiabatic pulses used. In this work adiabatic pulses having different modulation functions were utilized to generate T2ρ contrast in images of the human occipital lobe at magnetic field of 4 T. T2ρ time constants were measured using an adiabatic CP pulse sequence followed by an imaging readout. For these measurements, adiabatic full passage pulses of the hyperbolic secant HSn (n = 1 or 4) family having significantly different amplitude—and frequency—modulation functions were used with no time delays between pulses. A dynamic averaging (DA) mechanism (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities) alone was insufficient to fully describe differences in brain tissue water proton T2ρ time constants. Measurements of the apparent relaxation time constants (T  2† ) of brain tissue water as a function of the time between centers of pulses (τcp) at 4 and 7 T permitted separation of the DA contribution from that of dipolar relaxation. The methods presented assess T2ρ relaxation influenced by DA in tissue and provide a means to generate T2ρ contrast in MRI. Magn Reson Med 53:823–829, 2005.

T1ρ and T2ρ MRI in the evaluation of Parkinson’s disease

Prior work has shown that adiabatic T1ρ and T2ρ relaxation time constants may have sensitivity to cellular changes and the presence of iron, respectively, in Parkinson’s disease (PD). Further understanding of these magnetic resonance imaging (MRI) methods and how they relate to measures of disease severity and progression in PD is needed. Using T1ρ and T2ρ on a 4T MRI scanner, we assessed the substantia nigra (SN) of nine non-demented moderately affected PD and ten gender- and age-matched control participants. When compared to controls, the SN of PD subjects had increased T1ρ and reduced T2ρ. We also found a significant correlation between asymmetric motor features and asymmetry based on T1ρ. This study provides additional validation of T1ρ and T2ρ as a means to separate PD from control subjects, and T1ρ may be a useful marker of asymmetry in PD.

Rotating frame relaxation during adiabatic pulses vs. conventional spin lock: simulations and experimental results at 4 T

Spin relaxation taking place during radiofrequency (RF) irradiation can be assessed by measuring the longitudinal and transverse rotating frame relaxation rate constants (R(1rho) and R(2rho)). These relaxation parameters can be altered by utilizing different settings of the RF irradiation, thus providing a useful tool to generate contrast in MRI. In this work, we investigate the dependencies of R(1rho) and R(2rho) due to dipolar interactions and anisochronous exchange (i.e., exchange between spins with different chemical shift deltaomega not equal0) on the properties of conventional spin-lock and adiabatic pulses, with particular emphasis on the latter ones which were not fully described previously. The results of simulations based on relaxation theory provide a foundation for formulating practical considerations for in vivo applications of rotating frame relaxation methods. Rotating frame relaxation measurements obtained from phantoms and from the human brain at 4 T are presented to confirm the theoretical predictions.

Quantitative T1ρ and adiabatic Carr–Purcell T2 magnetic resonance imaging of human occipital lobe at 4 T

The feasibility of performing quantitative T1ρ MRI in human brain at 4 T is shown. T1ρ values obtained from five volunteers were compared with T2 and adiabatic Carr–Purcell (CP) T2 values. Measured relaxation time constants increased in order from T2, CP‐T2, T1ρ both in white and gray matter, demonstrating differential sensitivities of these methods to dipolar interactions and/or proton exchange and diffusion in local microscopic field gradients, which are so‐called dynamic averaging (DA) processes. In occipital lobe, all relaxation time constants were found to be higher in white matter than in gray matter, demonstrating contrast denoted as an “inverse transverse relaxation contrast.” This contrast persisted despite changing the delay between refocusing pulses or changing the magnitude of the spin‐lock field strength, which suggests that it does not originate from DA, as might be induced by the presence of Fe, but rather is related to dipolar interactions in the brain tissue. Magn Reson Med 54:14–19, 2005.

MRI contrast from relaxation along a fictitious field (RAFF)

A new method to measure rotating frame relaxation and to create contrast for MRI is introduced. The technique exploits relaxation along a fictitious field (RAFF) generated by amplitude‐ and frequency‐modulated irradiation in a subadiabatic condition. Here, RAFF is demonstrated using a radiofrequency pulse based on sine and cosine amplitude and frequency modulations of equal amplitudes, which gives rise to a stationary fictitious magnetic field in a doubly rotating frame. According to dipolar relaxation theory, the RAFF relaxation time constant (TRAFF) was found to differ from laboratory frame relaxation times (T1 and T2) and rotating frame relaxation times (T1ρ and T2ρ). This prediction was supported by experimental results obtained from human brain in vivo and three different solutions. Results from relaxation mapping in human brain demonstrated the ability to create MRI contrast based on RAFF. The value of TRAFF was found to be insensitive to the initial orientation of the magnetization vector. In the RAFF method, the useful bandwidth did not decrease as the train length increased. Finally, as compared with an adiabatic pulse train of equal duration, RAFF required less radiofrequency power and therefore can be more readily used for rotating frame relaxation studies in humans. Magn Reson Med, 2010.

Quantitative assessment of water pools by T 1 rho and T 2 rho MRI in acute cerebral ischemia of the rat.

The rotating frame longitudinal relaxation magnetic resonance imaging (MRI) contrast, T1ρ, obtained with on-resonance continuous wave (CW) spin-lock field is a sensitive indicator of tissue changes associated with hyperacute stroke. Here, the rotating frame relaxation concept was extended by acquiring both T1ρ and transverse rotating frame (T2ρ) MRI data using both CW and adiabatic hyperbolic secant (HSn; n = 1, 4, or 8) pulses in a rat stroke model of middle cerebral artery occlusion. The results show differences in the sensitivity of spinlock T1ρ and T2ρ MRI to detect hyperacute ischemia. The most sensitive techniques were CW-T1ρ and T1ρ using HS4 or HS8 pulses. Fitting a two-pool exchange model to the T1ρ and T2ρ MRI data acquired from the infarcting brain indicated time-dependent increase in free water fraction, decrease in the correlation time of water fraction associated with macromolecules, and increase in the exchange correlation time. These findings are consistent with known pathology in acute stroke, including vasogenic edema, destructive processes, and tissue acidification. Our results show that the sensitivity of the spinlock MRI contrast in vivo can be modified using different spinlock preparation blocks, and that physicochemical models of the rotating frame relaxation may provide insight into progression of ischemia in vivo.