MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease.

The cerebral deposition of amyloid beta-peptide, a central event in Alzheimer's disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high-field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1). transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of beta-amyloid in several brain regions, starting from 10 weeks of age; 2). transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of Abeta-peptide without beta-amyloid deposition; and 3). nontransgenic (NTg) littermates as controls. The transverse relaxation time T(2), an intrinsic MR parameter thought to reflect impaired cell physiology, was significantly reduced in the hippocampus, cingulate, and retrosplenial cortex, but not the corpus callosum, of PS-APP mice compared to NTg. No differences in T(1) values or proton density were detected between any groups of mice. These results indicate that T(2) may be a sensitive marker of abnormalities in this transgenic mouse model of AD.     

Passive staining: a novel ex vivo MRI protocol to detect amyloid deposits in mouse models of Alzheimer's disease.

Amyloid plaques are one of the hallmarks of Alzheimer's disease (AD). This study evaluated a novel microMRI strategy based on "passive staining" of brain samples by gadoteric acid. The protocol was tested at 4.7 T on control animals and APP/PS1 mice modeling AD lesions. T(1) was strongly decreased in passively stained brains. On high-resolution 3D gradient echo images, the contrast between the cortex and subcortical structures was highly improved due to a T2* effect. The brains of APP/PS1 mice revealed plaques as hypo-intense spots. They appeared larger in long compared to short TE images. This suggests that, after passive staining, plaques caused a susceptibility effect. This easily performed protocol is a complementary method to classic histology to detect the 3D location of plaques. It may also be used for the validation of in vivo MRI protocols for plaque detection by facilitating registration with histology via post mortem MRI.     

Visualization of beta-amyloid plaques in a transgenic mouse model of Alzheimer's disease using MR microscopy without contrast reagents.

The visualization of beta-amyloid plaque deposition in brain, a key feature of Alzheimer's disease (AD), is important for the evaluation of disease progression and the efficacy of therapeutic interventions. In this study, beta-amyloid plaques in the PS/APP transgenic mouse brain, a model of human AD pathology, were detected using MR microscopy without contrast reagents. beta-Amyloid plaques were clearly visible in the cortex, thalamus, and hippocampus of fixed brains of PS/APP mice. The distribution of plaques identified by MRI was in excellent agreement with those found in the immunohistological analysis of the same brain sections. It was also demonstrated that image contrast for beta-amyloid plaques was present in freshly excised nonfixed brains. Furthermore, the detection of beta-amyloid plaques was achieved with a scan time as short as 2 hr, approaching the scan time considered reasonable for in vivo imaging.     

Transverse relaxation time reflects brain amyloidosis in young APP/PS1 transgenic mice.

Amyloid deposits are one of the hallmarks of Alzheimer's disease (AD), one of the most devastating neurodegenerative disorders. In transgenic mice modeling Alzheimer's pathology, the MR transverse relaxation time (T(2)) has been described to be modulated by amyloidosis. This modification has been attributed to the age-related iron deposition that occurs within the amyloid plaques of old animals. In the present study, young APP/PS1 transgenic mice without histochemically detectable iron in the brain were specifically studied. In vivo measurements of T(2) in the hippocampus, at the level of the subiculum, were shown to reflect the density of amyloid plaques. This suggests that T(2) variations can be induced solely by aggregated amyloid deposits in the absence of associated histologically-detectable iron. Thus T(2) from regions with high amyloid load, such as the subiculum, is particularly well suited for following plaque deposition in young animals, i.e., at the earliest stages of the pathological process.     

In vivo quantitative whole-brain diffusion tensor imaging analysis of APP/PS1 transgenic mice using voxel-based and atlas-based methods

Introduction

Diffusion tensor imaging (DTI) has been applied to characterize the pathological features of Alzheimer's disease (AD) in a mouse model, although little is known about whether these features are structure specific. Voxel-based analysis (VBA) and atlas-based analysis (ABA) are good complementary tools for whole-brain DTI analysis. The purpose of this study was to identify the spatial localization of disease-related pathology in an AD mouse model.

Methods

VBA and ABA quantification were used for the whole-brain DTI analysis of nine APP/PS1 mice and wild-type (WT) controls. Multiple scalar measurements, including fractional anisotropy (FA), trace, axial diffusivity (DA), and radial diffusivity (DR), were investigated to capture the various types of pathology. The accuracy of the image transformation applied for VBA and ABA was evaluated by comparing manual and atlas-based structure delineation using kappa statistics. Following the MR examination, the brains of the animals were analyzed for microscopy.

Results

Extensive anatomical alterations were identified in APP/PS1 mice, in both the gray matter areas (neocortex, hippocampus, caudate putamen, thalamus, hypothalamus, claustrum, amygdala, and piriform cortex) and the white matter areas (corpus callosum/external capsule, cingulum, septum, internal capsule, fimbria, and optic tract), evidenced by an increase in FA or DA, or both, compared to WT mice (p?<?0.05, corrected). The average kappa value between manual and atlas-based structure delineation was approximately 0.8, and there was no significant difference between APP/PS1 and WT mice (p?>?0.05). The histopathological changes in the gray matter areas were confirmed by microscopy studies. DTI did, however, demonstrate significant changes in white matter areas, where the difference was not apparent by qualitative observation of a single-slice histological specimen.

Conclusion

This study demonstrated the structure-specific nature of pathological changes in APP/PS1 mouse, and also showed the feasibility of applying whole-brain analysis methods to the investigation of an AD mouse model.     

Longitudinal assessment of Alzheimer's beta-amyloid plaque development in transgenic mice monitored by in vivo magnetic resonance microimaging

PURPOSE: To assess the development of beta-amyloid (Abeta) plaques in the brain with age in the transgenic mouse model of Alzheimer's disease (AD) pathology by in vivo magnetic resonance microimaging (microMRI). MATERIALS AND METHODS: Live transgenic mice (Tg2576) and nontransgenic littermates (control) were studied at regular intervals between the ages of 12 and 18 months. Plaques were visualized using a T(2)-weighted rapid acquisition with relaxation enhancement (RARE) sequence. Changes in T(2) relaxation times were followed using a multislice multiecho (MSME) sequence. Plaque load and numerical density in MR images were calculated using SCIL image software. RESULTS: Abeta plaques were clearly detected with the T(2)-weighted RARE sequence in the hippocampal and cortical regions of the brain of Tg2576 mice but not in control mice. Following the plaque development in the same animals with age showed that plaque area, number, and size increased markedly, while T(2) relaxation time showed a decreasing trend with age. CONCLUSION: These results demonstrate that microMRI is a viable method for following the development of Abeta plaques in vivo, and suggest that this method may be feasible for assessing the effect of therapeutic interventions over time in the same animals.     

Method for reduced SAR T1rho-weighted MRI.

A reduced specific absorption rate (SAR) version of the T(1rho)-weighted MR pulse sequence was designed and implemented. The reduced SAR method employs a partial k-space acquisition approach in which a full power spin-lock pulse is applied to only the central phase-encode lines of k-space, while the remainder of k-space receives a low-power spin-lock pulse. Acquisition of high- and low-power phase-encode lines are interspersed chronologically to minimize average power deposition. In this way, the majority of signal energy in the central portion of k-space receives full T(1rho)-weighting, while the average SAR of the overall acquisition can be reduced, thereby lowering the minimum safely allowable TR. The pulse sequence was used to create T(1rho) maps of a phantom, an in vivo mouse brain, and the brain of a human volunteer. In the images of the human brain, SAR was reduced by 40% while the measurements of T(1rho) differed by only 2%. The reduced SAR sequence enables T(1rho)-weighted MRI in a clinical setting, even at high field strengths.     

Detection of Alzheimer's amyloid in transgenic mice using magnetic resonance microimaging.

The presence of amyloid-beta (Abeta) plaques in the brain is a hallmark pathological feature of Alzheimer's disease (AD). Transgenic mice overexpressing mutant amyloid precursor protein (APP), or both mutant APP and presenilin-1 (APP/PS1), develop Abeta plaques similar to those in AD patients, and have been proposed as animal models in which to test experimental therapeutic approaches for the clearance of Abeta. However, at present there is no in vivo whole-brain imaging method to detect Abeta plaques in mice or men. A novel method is presented to detect Abeta plaques in the brains of transgenic mice by magnetic resonance microimaging (muMRI). This method uses Abeta1-40 peptide, known for its high binding affinity to Abeta, magnetically labeled with either gadolinium (Gd) or monocrystalline iron oxide nanoparticles (MION). Intraarterial injection of magnetically labeled Abeta1-40, with mannitol to transiently open the blood-brain barrier (BBB), enabled the detection of many Abeta plaques. Furthermore, the numerical density of Abeta plaques detected by muMRI and by immunohistochemistry showed excellent correlation. This approach provides an in vivo method to detect Abeta in AD transgenic mice, and suggests that diagnostic MRI methods to detect Abeta in AD patients may ultimately be feasible.     

MRI and histological analysis of beta‐amyloid plaques in both human Alzheimer's disease and APP/PS1 transgenic mice

Purpose

To investigate the relationship between MR image contrast associated with beta‐amyloid (Aβ) plaques and their histology and compare the histopathological basis of image contrast and the relaxation mechanism associated with Aβ plaques in human Alzheimer's disease (AD) and transgenic APP/PS1 mouse tissues.

Materials and Methods

With the aid of the previously developed histological coil, T‐weighted images and R parametric maps were directly compared with histology stains acquired from the same set of Alzheimer's and APP/PS1 tissue slices.

Results

The electron microscopy and histology images revealed significant differences in plaque morphology and associated iron concentration between AD and transgenic APP/PS1 mice tissue samples. For AD tissues, T contrast of Aβ‐plaques was directly associated with the gradation of iron concentration. Plaques with significantly less iron load in the APP/PS1 animal tissues are equally conspicuous as the human plaques in the MR images.

Conclusion

These data suggest a duality in the relaxation mechanism where both high focal iron concentration and highly compact fibrillar beta‐amyloid masses cause rapid proton transverse magnetization decay. For human tissues, the former mechanism is likely the dominant source of R relaxation; for APP/PS1 animals, the latter is likely the major cause of increased transverse proton relaxation rate in Aβ plaques. The data presented are essential for understanding the histopathological underpinning of MRI measurement associated with Aβ plaques in humans and animals. J. Magn. Reson. Imaging 2009;29:997–1007. © 2009 Wiley‐Liss, Inc.     

Quantitative T1rho NMR spectroscopy of rat cerebral metabolites in vivo: effects of global ischemia.

The NMR relaxation times (T(1rho), T(2), and T(1)) of water, N-acetylaspartate (NAA), creatine (Cr), choline-containing compounds (Cho), and lactate (Lac) were quantified in rat brain at 4.7 T. In control animals, the cerebral T(1rho) figures, as determined with a spin-lock field of 1.0 G, were 575 +/- 30 ms, 380 +/- 19 ms, 705 +/- 53 ms, and 90 +/- 1 ms for NAA, Cr, Cho, and water, respectively. The T(1rho) figures were 62-103% longer than their respective T(2) values determined by a multiecho method. In global (ischemic) ischemia, T(1rho) of NAA declined by 34%, that of Cr and Cho did not change, and that of water increased by 10%. The T(1rho) of lactate in ischemic brain was 367 +/- 44 ms. Similar patterns of changes were observed in the multiecho T(2) of these cerebral metabolites. The T(1) of water and NAA changed in a fashion similar to that of T(1rho) and T(2). These results show differential responses in metabolite and water T(1rho) relaxation times following ischemia, and indicate that metabolite T(1rho) and T(2) relaxation times behave similarly in the ischemic brain. The contributions of dipolar and nondipolar effects on T(1rho) relaxation in vivo are discussed in this work.     

T 1 rho-relaxation mapping of human femoral-tibial cartilage in vivo

PURPOSE: To demonstrate the in vivo feasibility of measuring spin-lattice relaxation time in the rotating frame (T(1rho)); and T(1rho)-dispersion in human femoral cartilage. Furthermore, we aimed to compute the baseline T(1rho)-relaxation times and spin-lock contrast (SLC) maps on healthy volunteers, and compare relaxation times and signal-to-noise ratio (SNR) with corresponding T(2)-weighted images. MATERIALS AND METHODS: All MR imaging experiments were performed on a 1.5 T GE Signa scanner (GEMS, Milwaukee, WI) using a custom built 15-cm transmit-receive quadrature birdcage radio-frequency (RF) coil. The T(1rho)-prepared magnetization was imaged with a single-slice two-dimensional fast spin-echo (FSE) pulse sequence preencoded with a three-pulse cluster consisting of two hard 90 degrees pulses and a low power spin-lock pulse. T(1rho)-dispersion imaging was performed by varying the spin-lock frequency from 100 to 500 Hz in five steps in addition to varying the length of the spin-lock pulse. RESULTS: The average T(1rho)-relaxation times in the weight-bearing (WB) and nonweight-bearing (NWB) regions of the femoral condyle were 42.2 +/- 3.6 msec and 55.7 +/- 2.3 msec (mean +/- SD, N = 5, P < 0.0001), respectively. In the same regions, the corresponding T(2)-relaxation times were 31.8 +/- 1.5 msec and 37.6 +/- 3.6 msec (mean +/- SD, N = 5, P < 0.0099). T(1rho)-weighted images have approximately 20%-30% higher SNR than the corresponding T(2)-weighted images for similar echo time. The average SLC in the WB region of femoral cartilage was 30 +/-4.0%. Furthermore, SLC maps provide better contrast between fluid and articular surface of femoral-tibial joint than T(1rho)-maps. The T(1rho)-relaxation times varied from 32 msec to 42 msec ( approximately 31%) in the WB and 37 msec to 56 msec ( approximately 51%) in NWB regions of femoral condyle, respectively, in the frequency range 0-500 Hz (T(1rho)-dispersion). CONCLUSION: The feasibility of performing in vivo T(1rho) relaxation mapping in femoral cartilage at 1.5T clinical scanner without exceeding Food and Drug Administration (FDA) limits on specific absorption rate (SAR) of RF energy was demonstrated.     

APP/PS1转基因阿尔茨海默病小鼠的MR波谱定量分析

目的 利用MRS探讨APP/PS1转基因阿尔茨海默病(AD)小鼠脑内代谢物的变化及对早期AD的诊断价值.方法 35只APP/PS1双转基因AD小鼠(实验组)和20只野生型小鼠(对照组)分别在3、6、9月龄时采用7.0 T高场强MR仪行1H-MRS,测量小鼠大脑皮质及海马区N-乙酰天冬氨酸(NAA)、肌醇(mI)和肌酸(Cr)的峰下面积,计算NAA/Cr和mI/Cr比值,并与病理结果进行对照.分别以各月龄AD小鼠的NAA/Cr比值的95%可信区间的上限及mI/Cr比值的95%可信区间的下限作为阈值,比较其对AD小鼠的敏感度、特异度和准确度.两组间NAA/Cr和mI/Cr比值的比较采用独立样本t检验.结果 3、6、9月龄AD小鼠的mI/Cr比值分别为0.68±0.03、0.72±0.04、0.77±0.04,对照组分别为0.63±0.04、0.64±0.03、0.64±0.04,两组间差异均有统计学意义(t值分别为2.814、5.146、14.437,P值均<0.01),3月龄时ml/Cr比值即明显升高,病理检查显示大脑皮质及海马区出现星形胶质细胞的增生、活化;3、6、9月龄AD小鼠的NAA/Cr比值分别为1.17±0.08、1.04±0.05、0.90±0.05,对照组分别为1.18 ±0.07、1.16 ±0.07、1.18±0.08,3月龄时,两组间差异无统计学意义(t=0.752,P>0.05),6、9月龄时两组间差异有统计学意义(t值分别为-8.514、-5.646,P值均<0.05),6月龄时NAA/Cr比值明显降低,病理检查显示AB沉积斑块出现.mI诊断3、6及9月龄AD小鼠的敏感度分别为80%(28/35)、84%(26/31)、85%(23/27);特异度为85%(17/20)、94%(17/18)、100%(16/16);准确度为82%(45/55)、88%(43/49)、91%(39/43);NAA诊断6、9月龄AD小鼠的敏感度分别为84%(26/31)、89%(24/27);特异度为89%(16/18)、100%(16/16);准确性为86%(42/49)、93%(40/43).结论 mI、NAA是评价早期AD的高敏感度、高特异度的指标,且mI的变化早于NAA,1H-MRS定量分析为早期AD的诊断提供了重要依据.     

Indirect 17(O)-magnetic resonance imaging of cerebral blood flow in the rat.

Proton T(1rho)-dispersion MRI is demonstrated for indirect, in vivo detection of (17)O in the brain. This technique, which may be readily implemented on any clinical MRI scanner, is applied towards high-resolution, quantitative mapping of cerebral blood flow (CBF) in the rat by monitoring the clearance of (17)O-enriched water. Strategies are derived and employed for 1) quantitation of absolute H(2) (17)O tracer concentration from a ratio of high- and low-frequency spin-locked T(1rho) images, and 2) mapping CBF without having to transform the T(1rho) signal to H(2) (17)O tracer concentration. Absolute regional blood flow was mapped in a single 3-mm brain slice at an in-plane resolution of 0.4 x 0.8 mm within a 5-min tracer washout time; these data are consistent with the less localized CBF measurements reported in the literature. T(1rho)-weighted imaging yields excellent signal-to-noise ratios, spatiotemporal resolution, and anatomical contrast for mapping CBF.     

3D-T1rho quantitation of patellar cartilage at 3.0T

PURPOSE: To demonstrate the feasibility of three-dimensional (3D) T(1rho)-weighted imaging of human knee joint at 3.0T without exceeding the specific absorption rate (SAR) limits and the measurement of the baseline T(1rho) values of patellar cartilage and several muscles at the knee joint. MATERIALS AND METHODS: 3D gradient-echo sequence with a self-compensating spin-lock pulse cluster of 250 Hz power was used to acquire 3D-T(1rho)-weighted images of the knee joint of five healthy subjects. Global and regional analysis of patellar cartilage T(1rho) were performed. Furthermore, T(1rho) of several periarticular muscles were analyzed. RESULTS: The global average T(1rho) value of the patellar cartilage varied from 39 to 43 msec. The regional average T(1rho) values varied from 38 to 42 msec, and from 42 to 44 msec for medial and lateral facets, respectively. In vivo reproducibility of average T(1rho) of patellar cartilage was found to be 5% (coefficient of variation). Similarly, the global average T(1rho) values for biceps femoris, lateral gastrocnemius, medial gastrocnemius, and sartorius varied between 31-46, 29-49, 35-48, and 32-50 msec, respectively. CONCLUSION: We demonstrated the feasibility of 3D-T(1rho)-weighted imaging of the knee joint at 3.0T without exceeding SAR limits.     

T1rho-prepared balanced gradient echo for rapid 3D T1rho MRI

PURPOSE: To develop a T1rho-prepared, balanced gradient echo (b-GRE) pulse sequence for rapid three-dimensional (3D) T1rho relaxation mapping within the time constraints of a clinical exam (<10 minutes), examine the effect of acquisition on the measured T1rho relaxation time and optimize 3D T1rho pulse sequences for the knee joint and spine. MATERIALS AND METHODS: A pulse sequence consisting of inversion recovery-prepared, fat saturation, T1rho-preparation, and b-GRE image acquisition was used to obtain 3D volume coverage of the patellofemoral and tibiofemoral cartilage and lower lumbar spine. Multiple T1rho-weighted images at various contrast times (spin-lock pulse duration [TSL]) were used to construct a T1rho relaxation map in both phantoms and in the knee joint and spine in vivo. The transient signal decay during b-GRE image acquisition was corrected using a k-space filter. The T1rho-prepared b-GRE sequence was compared to a standard T1rho-prepared spin echo (SE) sequence and pulse sequence parameters were optimized numerically using the Bloch equations. RESULTS: The b-GRE transient signal decay was found to depend on the initial T1rho-preparation and the corresponding T1rho map was altered by variations in the point spread function with TSL. In a two compartment phantom, the steady state response was found to elevate T1rho from 91.4+/-6.5 to 293.8+/-31 and 66.9+/-3.5 to 661+/-207 with no change in the goodness-of-fit parameter R2. Phase encoding along the longest cartilage dimension and a transient signal decay k-space filter retained T1rho contrast. Measurement of T1rho using the T1rho-prepared b-GRE sequence matches standard T1rho-prepared SE in the medial patellar and lateral patellar cartilage compartments. T1rho-preparedb-GRE T1rho was found to have low interscan variability between four separate scans. Mean patellar cartilage T1rho was elevated compared to femoral and tibial cartilage T1rho. CONCLUSION: The T1rho-prepared b-GRE acquisition rapidly and reliably accelerates T1rho quantification of tissues offset partially by a TSL-dependent point spread function.     

T1rho imaging of murine brain tumors at 4 T

RATIONALE AND OBJECTIVES: The goal of this study was to evaluate the utility of T1rho weighting in magnetic resonance imaging of murine brain tumors. MATERIALS AND METHODS: S91 Cloudman melanoma was implanted in mouse brains (n = 4). A T2-weighted spin-echo (SE) and a T1rho-weighted fast SE-based sequence were performed on a 4-T clinical imager. T2 and T1rho maps were computed. The tumor-to-normal-tissue contrast was compared between T2-weighted, T1rho-weighted, proton-density-weighted, and pre- and postcontrast T1-weighted SE images. RESULTS: The tumor-tissue contrast of the T1rho-weighted images was similar to that of the T2-weighted images but less than that of the postcontrast T1-weighted images. The T1rho-weighted images provided better definition of tumor boundaries than T2-weighted images. At spin-locking powers of 0.5 and 1.5 kHz, the T1rho of the tumor was 64.0 msec +/- 0.46 and 68.65 msec +/- 0.59, respectively. There was no significant inter- or intra-animal variation in T1rho for tumor or normal brain cortex. CONCLUSION: T1rho-weighted imaging performed at low spin-lock strengths qualitatively depicted tumor borders better than proton-density or T2-weighted imaging and could be useful in treatment planning when combined with other imaging sequences.     

T2 and T1rho MRI in articular cartilage systems.

T2 and T1rho have potential to nondestructively detect cartilage degeneration. However, reports in the literature regarding their diagnostic interpretation are conflicting. In this study, T2 and T1rho were measured at 8.5 T in several systems: 1) Molecular suspensions of collagen and GAG (pure concentration effects): T2 and T1rho demonstrated an exponential decrease with increasing [collagen] and [GAG], with [collagen] dominating. T2 varied from 90 to 35 ms and T1rho from 125 to 55 ms in the range of 15-20% [collagen], indicating that hydration may be a more important contributor to these parameters than previously appreciated. 2) Macromolecules in an unoriented matrix (young bovine cartilage): In collagen matrices (trypsinized cartilage) T2 and T1rho values were consistent with the expected [collagen], suggesting that the matrix per se does not dominate relaxation effects. Collagen/GAG matrices (native cartilage) had 13% lower T2 and 17% lower T1rho than collagen matrices, consistent with their higher macromolecular concentration. Complex matrix degradation (interleukin-1 treatment) showed lower T2 and unchanged T1rho relative to native tissue, consistent with competing effects of concentration and molecular-level changes. In addition, the heterogeneous GAG profile in these samples was not reflected in T2 or T1rho. 3) Macromolecules in an oriented matrix (mature human tissue): An oriented collagen matrix (GAG-depleted human cartilage) showed T2 and T(1rho) variation with depth consistent with 16-21% [collagen] and/or fibril orientation (magic angle effects) seen on polarized light microscopy, suggesting that both hydration and structure comprise important factors. In other human cartilage regions, T2 and T1rho abnormalities were observed unrelated to GAG or collagen orientation differences, demonstrating that hydration and/or molecular-level changes are important. Overall, these studies illustrate that T2 and T1rho are sensitive to biologically meaningful changes in cartilage. However, contrary to some previous reports, they are not specific to any one inherent tissue parameter.     

T1rho relaxation mapping in human osteoarthritis (OA) cartilage: comparison of T1rho with T2

PURPOSE: To quantify the spin-lattice relaxation time in the rotating frame (T1rho) in various clinical grades of human osteoarthritis (OA) cartilage specimens obtained from total knee replacement surgery, and to correlate the T1rho with OA disease progression and compare it with the transverse relaxation time (T2). MATERIALS AND METHODS: Human cartilage specimens were obtained from consenting patients (N = 8) who underwent total replacement of the knee joint at the Pennsylvania Hospital, Philadelphia, PA, USA. T2- and T1rho-weighted images were obtained on a 4.0 Tesla whole-body GE Signa scanner (GEMS, Milwaukee, WI, USA). A 7-cm diameter transmit/receive quadrature birdcage coil tuned to 170 MHz was employed. RESULTS: All of the surgical knee replacement OA cartilage specimens showed elevated relaxation times (T2 and T1rho) compared to healthy cartilage tissue. In various grades of OA specimens, the T1rho relaxation times varied from 62 +/- 5 msec to 100 +/- 8 msec (mean +/- SEM) depending on the degree of cartilage degeneration. However, T2 relaxation times varied only from 32 +/- 2 msec to 45 +/- 4 msec (mean +/- SEM) on the same cartilage specimens. The increase in T2 and T1rho in various clinical grades of OA specimens were approximately 5-50% and 30-120%, respectively, compared to healthy specimens. The degenerative status of the cartilage specimens was also confirmed by histological evaluation. CONCLUSION: Preliminary results from a limited number of knee specimens (N = 8) suggest that T1rho relaxation mapping is a sensitive noninvasive marker for quantitatively predicting and monitoring the status of macromolecules in early OA. Furthermore, T1rho has a higher dynamic range (>100%) for detecting early pathology compared to T2. This higher dynamic range can be exploited to measure even small macromolecular changes with greater accuracy compared to T2. Because of these advantages, T1rho relaxation mapping may be useful for evaluating early OA therapy.     

Application of the keyhole technique to T1rho relaxation mapping

PURPOSE: To demonstrate the feasibility of using the keyhole technique to minimize error in a least squares regression estimation of T(1rho) from magnetic resonance (MR) image data. MATERIALS AND METHODS: The keyhole method of partial k-space acquisition was simulated using data from a virtual phantom and MR images of ex vivo bovine and in vivo human cartilage. T(1rho) maps were reconstructed from partial k-space (keyhole) image data using linear regression, and error was measured with relation to T(1rho) maps created from the full k-space images. An error model was created based on statistical theory and fitted to the error measurements. RESULTS: T(1rho) maps created from keyhole images of a human knee produced levels of error on the order of 1% while reducing standard image acquisition time approximately by half. The resultant errors were strongly correlated with expectations derived from statistical theory. CONCLUSION: The error model can be used to analytically optimize the keyhole method in order to minimize the overall error in the estimation of the relaxation parameter of interest. The keyhole method can be generalized to significantly expedite all forms of relaxation mapping.     

Three-dimensional T1rho-weighted MRI at 1.5 Tesla

PURPOSE: To design and implement a magnetic resonance imaging (MRI) pulse sequence capable of performing three-dimensional T(1rho)-weighted MRI on a 1.5-T clinical scanner, and determine the optimal sequence parameters, both theoretically and experimentally, so that the energy deposition by the radiofrequency pulses in the sequence, measured as the specific absorption rate (SAR), does not exceed safety guidelines for imaging human subjects. MATERIALS AND METHODS: A three-pulse cluster was pre-encoded to a three-dimensional gradient-echo imaging sequence to create a three-dimensional, T(1rho)-weighted MRI pulse sequence. Imaging experiments were performed on a GE clinical scanner with a custom-built knee-coil. We validated the performance of this sequence by imaging articular cartilage of a bovine patella and comparing T(1rho) values measured by this sequence to those obtained with a previously tested two-dimensional imaging sequence. Using a previously developed model for SAR calculation, the imaging parameters were adjusted such that the energy deposition by the radiofrequency pulses in the sequence did not exceed safety guidelines for imaging human subjects. The actual temperature increase due to the sequence was measured in a phantom by a MRI-based temperature mapping technique. Following these experiments, the performance of this sequence was demonstrated in vivo by obtaining T(1rho)-weighted images of the knee joint of a healthy individual. RESULTS: Calculated T(1rho) of articular cartilage in the specimen was similar for both and three-dimensional and two-dimensional methods (84 +/- 2 msec and 80 +/- 3 msec, respectively). The temperature increase in the phantom resulting from the sequence was 0.015 degrees C, which is well below the established safety guidelines. Images of the human knee joint in vivo demonstrate a clear delineation of cartilage from surrounding tissues. CONCLUSION: We developed and implemented a three-dimensional T(1rho)-weighted pulse sequence on a 1.5-T clinical scanner.