In vivo quantification of citrate concentration and water T2 relaxation time of the pathologic prostate gland using H MRS and MRI

We have previously reported a striking correlation between water T₂ relaxation time and citrate concentration in the normal prostate (Liney G.P.; Lowry M.; Turnbull L.W.; Manton D.J.; Knowles A.J.; Blackband S.J.; Horsman A. Proton MR T₂ maps correlate with the citrate concentration in the prostate. NMR Biomed. 9:59–64; 1996). In this study we present data from similar studies of the pathologic gland. The findings support the hypothesis that measurement of both citrate concentration and water T₂ relaxation time in vivo may aid the differentiation of prostatic carcinoma from benign disease and normal tissue.     

Diet and gastrointestinal signal on T1-weighted magnetic resonance imaging of mice

In magnetic resonance (MR) imaging of small animals, the gastrointestinal contents may give rise to intense signals on T1-weighted images. The aim of this study was to determine the optimal dietary preparation to reduce gastrointestinal signals in mice and to evaluate the usefulness of this approach. Images of the mouse trunk were obtained using a T1-weighted, three-dimensional fast low-angle shot sequence under various dietary conditions and were compared with respect to the gastrointestinal signals and image quality. The dietary preparation studied included giving alternative diets for 24 h, intestinal cleansing, and 6-h fasting. Mice with and without dietary preparation underwent MR lymphography using gadofluorine 8, and the visualization of abdominal lymph nodes was compared. In the absence of dietary preparation, hyperintense areas were conspicuous in the gastrointestinal system, whereas on the images taken from mice fed potato or sweet potato for 24 h before imaging, gastrointestinal hyperintensity was less prominent. This preparation also reduced artifactual signals and resulted in higher-quality images of the kidneys. Intestinal cleansing, which consisted of 24-h fasting and laxative intake, did not reduce the gastrointestinal signals and caused signal changes that were indicative of fatty liver development. Some of the abdominal lymph nodes of the mice that did not receive dietary preparation were visualized on MR lymphography source images but not on maximum intensity projection (MIP) images. In contrast, on the MIP images of mice fed potato, all the lymph nodes delineated on the source images were successfully visualized. In conclusion, feeding mice potato or sweet potato for 24 h before MR imaging reduces the gastrointestinal signals and image degradation due to artifacts. Appropriate dietary preparations facilitate the display of target structures on MIP images and are expected to enhance the capabilities of small animal MR imaging.     

Analysis of feasibility of in vitro nuclear magnetic resonance tracking human umbilical cord mesenchymal stem cells by Gd-DTPA labeled

Objective

Three different kinds of transfection reagents were used to mediate the transfection of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) into human umbilical-cord-derived mesenchymal stem cells (hUCMSCs). The efficacy of different transfection reagents and the feasibility of NMR tracer in vitro of magnetized stem cells were estimated.

Methods

After purification by tissue explants adherent method, the biological characteristics of hUCMSCs in vitro were identified by subculture and amplification. Calcium phosphate, Effectene and liposome2000 were used to transfect Gd-DTPA-labeled hUCMSCs respectively, and cell counting was used to mediate the transfection of Gd-DTPA into hUCMSCs, which were then induced to lipoblast and osteoblast in vitro. The determination of the transfection activities of the transfection reagents was conducted by measuring the magnetic resonance imaging (MRI) signal intensity of the Gd-DTPA-labeled cells and the concentration of gadolinium ion in the cells. Furthermore, the relationship between the signal intensity of Gd-DTPA-labeled hUCMSCsMRI, cell subculture and generations was studied.

Results

Primary cells were obtained by tissue explants adherent for two weeks. The cells displayed a long spindle form and grew in swirl. After two passage generations, the cellular morphology became more homogeneous. The result detected by the flow cytometer showed that CD29C, D44, CD90, and CD105 were highly expressed, while no CD45, CD40, and HLA-DR expression was detected in the third generation cells. Directional induction in vitro caused the differentiation into lipoblast and osteoblast. After transfected by calcium phosphate, Effectene and liposome 2000, the signal intensity of stem cells was 2281.2 ± 118.8, 2031.9 ± 59.7 and 1887.4 ± 40.8 measured by MRI. Differences between these three groups were statistically significant (P < 0.05). The concentrations of gadolinium ion in three groups of stem cells were 0.178 ± 0.009 mg/L, 0.158 ± 0.003 mg/L and 0.120 ± 0.002 mg/L respectively, examined by inductively coupled plasma atomic emission spectrometry. No significant differences were found among these three groups (P < 0.05). The proliferation and differentiation abilities of the Gd-DTPA-labeled stem cells were not affected. A minimum 5 × 10⁴ Gd-DTPA-labeled stem cells could be traced with MRI in vitro and presented in high signal. The trace duration time in vitro was about 12 days.

Conclusions

Tissue explants adherent method can be availably applied to purify hUCMSCs. The Effectene method was proved to have the best transfection effect. The proliferation ability and differentiation potency of Gd-DTPA-labeled hUCMSCs were not affected, and the NMR of labeled stem cells in vitro was proved to be feasible.     

In vivo sodium-23 magnetic resonance surface coil imaging: Observing experimental cerebral ischemia in the rat

Sodium-23 magnetic resonance imaging can be used to detect and assess experimental cerebral ischemia in the rat. An imaging technique utilizing a surface coil is described to produce sodium magnetic resonance images of good quality and resolution within 10 min. A novel method of hemispheric occlusion showed edema in the right brain of the rat head within 3 hr after injury. The edema was especially pronounced by 12 hr with effects in the right brain, eye and surrounding muscle evident.     

The application of proton nuclear magnetic resonance imaging for the in vivo characterisation of chemically induced renal lesions in rats over a prolonged time study

Renal cortical and medullary spin-lattice (T₁) relaxation times were measured at various time points over a period of 56 days following the administration of a single i.p. injection of 100 mg/kg 2-bromoethanamine hydrobromide (BEA), 200 mg/kg hexachloro-1,3-butadiene (HCBD) or 100 mg/kg puromycin aminonucleoside (PAN) to male Wistar rats. Administration of a single injection of HCBD caused a dramatic, immediate rise in the cortical T₁ values above control values, and these levels remained elevated until, by Day 28 postinjection the levels were back to control values. Administration of BEA also caused an elevation in cortical T₁ values, but in this case these values remained above control values for the rest of the study. The administration of PAN did not produce any significant increases in cortical T₁ values until 14 days postinjection. The elevated T₁ values remained above control values for the rest of the study. These increases observed in cortical T₁ values appeared to be mirrored by decreases in medullary T₁ values. Increases in cortical T₁ values were accompanied by visual changes in the NMR images and enlargement of the kidneys. The histological findings were consistent with the NMR data, confirming that morphologically the tissues did show a full recovery by Day 28 in the HCBD-treated animals. This was not the case following injection of both BEA and PAN, where necrosis was not reversible and there was no recovery of the tissues.     

In vivo MRI reveals the dynamics of pathological changes in the brains of cathepsin D-deficient mice and correlates changes in manganese-enhanced MRI with microglial activation

Cathepsin D (CTSD; EC 3.4.23.5) is essential for normal development and/or maintenance of neurons in the central nervous system: its deficiency causes a devastating neurological disorder with severely shortened life span in man, sheep and mouse. Neuropathologically, the CTSD deficiencies are characterized by selective neuronal degeneration, gliosis and accumulation of autofluorescent proteinaceous storage material in neurons. Our aim was to study the dynamics behind the pathological alterations occurring in the brains of CTSD-deficient (CTSD-/-) mice by using in vivo magnetic resonance imaging (MRI) and histology. In order to do this, we measured T(2) signal intensity (SI), apparent diffusion coefficient, area and volume of multiple brain structures from MR images acquired using T(2)-, T(1)- and diffusion-weighted sequences at three time points during disease progression. MRI revealed no differences in the brains between CTSD-/- and control mice at postnatal day 15+/-1 (P15+/-1), representing an initial stage of the disease. In the intermediate stage of the disease, P19(+/-1), SI alterations in the thalami of the affected mice became evident in both T(1)- and T(2)-weighted images. The terminal stage of the disease, P25, was characterized by marked alterations in the T(2) SI, apparent diffusion coefficient and volume of multiple brain structures in CTSD-/- mice. In addition, manganese enhanced high-resolution T(1)-weighted 3D sequences (MEMRI) and histological stainings revealed that the hyperintense signal areas in MEMRI matched perfectly with areas of microglial activation in the brains of CTSD-/- mice at the terminal disease stage. In conclusion, the SI alterations in the thalami of CTSD-/- mice preceded other changes, and the degenerative process was greatly enhanced at the age P19(+/-1), leading to severely reduced brain volume in just 6 days.     

The physiology and metabolism of neuronal activation: in vivo studies by NMR and other methods

In this article, a review is made of the current knowledge concerning the physiology and metabolism of neuronal activity, as provided by the application of NMR approaches in vivo. The evidence furnished by other functional spectroscopic and imaging techniques, such as PET and optical methods, are also discussed. In spite of considerable amounts of studies presented in the literature, several controversies concerning the mechanisms underlying brain function still remain, mainly due to the difficult assessment of the single vascular and metabolic dynamics which generally influence the functional signals. In this framework, methodological and technical improvements are required to provide new and reliable experimental elements, which can support or eventually modify the current models of activation.     

Localized in vivo proton spectroscopy of the bone marrow in patients with leukemia

Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate the haemopoietic (iliac bone) and fatty bone marrow (tibia) in patients with leukemia and polycythaemia vera. Selective measurements of the relaxation times T₁ and T₂ for the “water” and “fat” resonances in the bone marrow spectra were performed. Nine patients with acute leukemia and three patients with chronic leukemia were examined at diagnosis. Three patients with acute leukemia in remission were also examined. Five of the leukemic patients had follow-up examinations performed in relation to chemotherapeutic treatment. Nine patients with polycythaemia vera and 21 normal control subjects were examined with identical methods for comparison. All patients had bone marrow biopsies performed prior to every MR examination. Significant differences could be detected in the spectral patterns from iliac bone marrow in patients with leukemia at diagnosis compared to the healthy normal controls. The “relative water content” was increased in the iliac bone marrow spectra of the leukemic patients compared to the normal subjects, which indicates an increase in the amount of haemopoietic tissue and a corresponding decrease in marrow fat content. The T₁ relaxation times of the “water” resonance in the spectra from the iliac bone marrow of the leukemic patients were significantly prolonged at diagnosis, compared to the normal controls and the patients with polycythaemia vera. After chemotherapeutic induction of remission, the spectra from the iliac bone marrow in the patients with leukemia resembled normal spectra. Four leukemic patients had abnormal spectra from the tibial bone marrow and one patients showed early changes in tibial marrow during chemotherapeutic treatment, before any major changes could be detected in the iliac bone marrow.     

The resonance decay function method in the determination of the pre-factor of the Néel relaxation time of single-domain nanoparticles

In its simple form, the relaxation time of the Néel relaxation process of the magnetic moment of single-domain particles is given by τ_N=τ_0Nexp(σ), σ being the ratio of anisotropy energy to thermal energy. The pre-factor, τ_0N, is normally given a value of 10⁻⁹ s, but values ranging from 10⁻⁸ to 10⁻¹² s have been reported in literature. Here, by means of the field and frequency dependence of the complex magnetic susceptibility, χ(ω,H)=χ′(ω,H)−iχ″(ω,H), of a magnetic fluid sample, in the MHz-GHz range, in conjunction with the determination of the sample decay function, b(t), the pre-factor τ_0N is determined. b(t) is readily obtained through the inverse Fourier transformation relationship, which exists between b(t) and χ″(ω).     

Diffusion tensor fiber tractography of the olfactory tract

Magnetic resonance diffusion tensor imaging with fiber tracking is used for 3-dimensional visualization of the nervous system. Peripheral nerves and all cranial nerves, except for the olfactory tract, have previously been visualized. The olfactory tracts are difficult to depict with diffusion-weighted imaging due to the high sensitivity to susceptibility artifacts at the base of the skull. Here we report an optimized single-shot diffusion-weighted echo planar imaging sequence that can visualize the olfactory tracts with fiber tracking. Five healthy individuals were examined, and the olfactory tracts could be fiber tracked with the diffusion-weighted sequence. For comparison and as a negative control, an anosmic patient was examined. No olfactory tracts were visualized on T2-weighted nor diffusion-weighted fiber tracking images. Measuring diffusion in the olfactory tracts promise to facilitate the identification of different hyposmic and anosmic conditions.     

Technical evaluation of in vivo abdominal fat and IMCL quantification using MRI and MRSI at 3 T

OBJECTIVES: The objectives of this study were to develop protocols that measure abdominal fat and calf muscle lipids with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), respectively, at 3 T and to examine the correlation between these parameters and insulin sensitivity. MATERIALS AND METHODS: Ten nondiabetic subjects [five insulin-sensitive (IS) subjects and five insulin-resistant (IR) subjects] were scanned at 3 T. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were segmented semiautomatically from abdominal imaging. Intramyocellular lipids (IMCL) in calf muscles were quantified with single-voxel MRS in both soleus and tibialis anterior muscles and with magnetic resonance spectroscopic imaging (MRSI). RESULTS: The average coefficient of variation (CV) of VAT/(VAT+SAT) was 5.2%. The interoperator CV was 1.1% and 5.3% for SAT and VAT estimates, respectively. The CV of IMCL was 13.7% in soleus, 11.9% in tibialis anterior and 2.9% with MRSI. IMCL based on MRSI (3.8+/-1.2%) were significantly inversely correlated with glucose disposal rate, as measured by a hyperinsulinemic-euglycemic clamp. VAT volume correlated significantly with IMCL. IMCL based on MRSI for IR subjects was significantly greater than that for IS subjects (4.5+/-0.9% vs. 2.8+/-0.5%, P=.02). CONCLUSION: MRI and MRS techniques provide a robust noninvasive measurement of abdominal fat and muscle IMCL, which are correlated with insulin action in humans.     

In vivo proton magnetic resonance spectroscopy of alcohol in rhesus monkey brain

Brain alcohol was measured in rhesus monkeys (Macaca mulatta) by proton magnetic resonance spectroscopy (MRS) following acute nasogastric alcohol administration (0.8 g/kg). Monkeys were anesthetized with ketamine and xylazine. A 1.5 T whole body imager and a 3-inch surface coil were used to acquire TE 30 and 270 ms spectra from a 7.5 cc voxel localized with a stimulated echo (STEAM) sequence. Venous blood samples were collected during spectral acquisitions for gas chromatographic determination of temporally concordant blood alcohol levels (BALs). Acute alcohol administration did not alter the resonance areas of N-acetylaspartate/N-acetyl containing compounds (NAA), choline containing compounds, or total creatine. The NAA resonance was used as an internal standard to calculate approximate brain alcohol concentrations, which averaged 27 ± 3% and 27 ± 8% of temporally concordant BALs (T₂-corrected TE 30 and TE 270 ms spectra, respectively). In addition to reconfirming results from prior studies finding incomplete detection of brain alcohol with MRS, these results demonstrate the feasibility of measuring brain alcohol in anesthetized nonhuman primates to examine relationships between alcohol exposure history and MRS-visibility of brain alcohol.     

Research and progress in magnetic resonance imaging of triple-negative breast cancer

Triple-negative breast cancer (TNBC), which characterized by distinct biological and clinical pathological features, has a worse prognosis because the lack of effective therapeutic targets. Breast MR is the most accurate imaging modality for diagnosis of breast cancer currently. MR imaging recognition could assist in diagnosis, pretreatment planning and prognosis evaluation of TNBC. MR findings of a larger solitary lesion, mass with smooth mass margin, high signal intensity on T₂-weighted images and rim enhancement are typical MRI features associated with TNBC. Further work is necessary about the clinical application of dynamic contrast-enhanced MR imaging (DCE-MRI), DWI and MRS.     

Contrast-material-enhanced MR urography in evaluation of postoperative lower urinary tract fistulae and leakages

Urinary fistulas and leakages of lower urinary tract are serious complications of various surgical procedures. Radiologists need to have enough information about these situations to perform precise diagnosis and treatment. Various techniques [such as intravenous pyelography, ultrasound, computed tomography (CT), CT urography, cystoscopy, cystography and magnetic resonance (MR) imaging] are used for the diagnosis of these conditions. Application of all these techniques reduces the comfort and cooperation of the patients and increases the cost. Here we present four postoperative patients with lower urinary tract fistula or leakage. To the best of our knowledge, there is no report regarding the use of contrast-material-enhanced MR urography (CE-MRU) in the demonstration of postoperative lower urinary tract fistulae and leakages. In conclusion, CE-MRU could show the existence and location of the urinary fistulae and leakages clearly without the need for another investigation technique, as described in our patients. Also, CE-MRU is a safe and relatively inexpensive technique that avoids exposure to radiation as well as nephrotoxic and more allergic contrast-material administration.     

A model for quantitative changes in the magnetic resonance parameters of muscle in children after therapeutic irradiation

Purpose/ObjectiveThis study aimed to develop objective models of radiation effects on musculature in children with soft tissue sarcoma using treatment dosimetry and clinical and quantitative magnetic resonance imaging (MRI) parameters that may be used to guide treatment planning or predict side effects.MethodsIn the initial 13 patients undergoing external beam radiation therapy (RT) on a Phase II study of conformal or intensity-modulated RT for the treatment of soft tissue sarcoma approved by an Institutional Review Board, we evaluated quantitative MRI changes in the musculature to assess radiation-related treatment effects. Patients with soft tissue sarcoma, including Ewing's sarcoma, had quantitative T₁, T₂ and dynamic enhanced MRI (DEMRI) performed before, during (Week 4) and after RT (Week 12). Regions of interest were selected in consistent locations within and outside the high-dose regions (on ipsilateral and contralateral sides when available). Mean RT dose, T₁, T₂ and DEMRI parameters were calculated and modeled using a mixed random coefficient dose model.ResultsThe mean doses to the high- and low-dose regions were 56.4 Gy (41.8–75.3 Gy) and 13.0 Gy (0.1–37.5 Gy), respectively. Compared with tissues distant from the tumor bed, maximal enhancement was significantly increased in tissues adjacent to the tumor/tumor bed prior to RT (60.6 vs. 44.2, P=.045) and remained elevated after 12 weeks. T₁ was significantly elevated in tissues adjacent to the tumor bed prior to RT (942.4 vs. 759.0, P=.0078). The slope of longitudinal change in T₁ was greater for tissues that received low-dose irradiation than those that received high-dose irradiation (P=.0488). The effect of dose on the slope of T₂ was different (P=.0333) when younger and older patients are compared.ConclusionsAcute affects of irradiation in muscle are quantifiable via MRI. These models provide evidence that quantifiable MRI parameters may be correlated with patient parameters of radiation dose and clinical factors including patient age. Long-term follow-up will be required to determine if acute changes correlate with clinically significant late effects.     

Diffusion-weighted MR imaging for assessing synovitis of wrist and hand in patients with rheumatoid arthritis: A feasibility study

The purpose of this study was to investigate the feasibility of diffusion-weighted imaging (DWI) in detecting synovitis of wrist and hand in patients with rheumatoid arthritis (RA) and evaluate its sensitivity, specificity and accuracy as compared to T₂-weighted imaging (T2WI) with short tau inversion recovery (STIR) with the reference standard contrast-enhanced magnetic resonance imaging (CE-MRI). Twenty-five patients with RA underwent MR examinations including DWI, T2WI with STIR and CE-MRI. MR images were reviewed for the presence and location of synovitis of wrist and hand. The sensitivity, specificity and accuracy of DWI and T2WI with STIR were calculated respectively and then compared. All patients included in this study completed MR examinations and yielded diagnostic image quality of DWI. For individual joint, there was good to excellent inter-observer agreement (k = 0.62–0.83) using DWI images, T2WI with STIR images and CE-MR images, respectively. There was a significance between DWI and T2WI with STIR in analyzing proximal interphalangeal joints II–V, respectively (P < 0.05). The k-values for the detection of synovitis indicated excellent overall inter-observer agreements using DWI images (k = 0.86), T2WI with STIR images (k = 0.85) and CE-MR images (k = 0.91), respectively. Overall, DWI demonstrated a sensitivity, specificity and accuracy of 75.6%, 89.3% and 84.6%, respectively, for detection of synovitis, while 43.0%, 95.7% and 77.6% for T2WI with STIR, respectively. DWI showed positive lesions much better and more than T2WI with STIR. Our results indicate that DWI presents a novel non-invasive approach to contrast-free imaging of synovitis. It may play a role as an addition to standard protocols.     

In vivo measurement of normal rat intracellular pyruvate and lactate levels after injection of hyperpolarized [1-(13)C]alanine

Hyperpolarized technology utilizing dynamic nuclear polarization has enabled rapid and high-sensitivity measurements of ¹³C metabolism in vivo. The most commonly used in vivo agent for hyperpolarized ¹³C metabolic imaging thus far has been [1-¹³C]pyruvate. In preclinical studies, not only is its uptake detected, but also its intracellular enzymatic conversion to metabolic products including [1-¹³C]lactate and [1-¹³C]alanine. However, the ratio of ¹³C-lactate/¹³C-pyruvate measured in this data does not accurately reflect cellular values since much of the [1-¹³C]pyruvate is extracellular depending on timing, vascular properties, and extracellular space and monocarboxylate transporter activity. In order to measure the relative levels of intracellular pyruvate and lactate, in this project we hyperpolarized [1-¹³C]alanine and monitored the in vivo conversion to [1-¹³C]pyruvate and then the subsequent conversion to [1-¹³C]lactate. The intracellular lactate-to-pyruvate ratio of normal rat tissue measured with hyperpolarized [1-¹³C]alanine was 4.89±0.61 (mean±S.E.) as opposed to a ratio of 0.41±0.03 when hyperpolarized [1-¹³C]pyruvate was injected.     

Phantom and in vivo study of the Look-Locher T1 mapping method

This paper describes and tests the LL-EPI method for obtaining quantitative T₁ estimates in a few seconds thereby allowing dynamic T₁ studies. It is shown that the method works even when there is an inflow into the imaged volume, e.g., in a vessel. No calibration is needed. The method has been tested in a phantom study with several different scan parameter set-ups, with and without inflow. The method shows robustness and individual scan parameters and inflow rates do not influence the ability to calculate the Gd-DTPA concentration. Linearity prevail between the measured 1/T₁ and the Gd-DTPA concentration in the range 150 < T₁ < 2500 ms. In a dynamic Gd-DTPA phantom study, it was shown that the dynamic LL-EPI T₁ mapping technique was three times more sensitive than the signal from a T^*₂-weighted EPI sequence. In an in vivo study, dynamic T₁ mapping of the Gd-DTPA uptake in a meningioma was performed. Inspection of the uptake curves indicates that the method is feasible in clinical perfusion studies.