Differentiation of follicular carcinomas from adenomas using histogram obtained from diffusion-weighted MRI.

AIM: To evaluate the role of histogram analysis of apparent diffusion coefficient (ADC) maps from diffusion-weighted imaging (DWI) in the differentiation of follicular thyroid carcinoma (FTC) from follicular adenoma (FA) in nodules indeterminate on ultrasound-guided core needle biopsy (USCNB). MATERIALS AND METHODS: This study was performed with institutional review board approval. Seventeen patients who were planned to undergo diagnostic lobectomy for an indeterminate thyroid nodule (atypical of unknown significance/follicular lesion of undetermined significance [AUS/FLUS] or suspicious for follicular neoplasm/follicular neoplasm [SFN]) on USCNB were enrolled prospectively. All patients underwent DWI on the day before surgery. Histogram parameters were derived from ADC values obtained from the whole extent of the tumours. The parameters were compared with the final diagnosis based on histopathological examination after surgery. The accuracy of the parameters in differentiating FTC from FA was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Twelve patients were confirmed as having FA and five patients as having FTC. Histogram parameters including the 10th (ADC10), 25th (ADC25), and 50th (ADC50) percentiles of the ADC values were significantly lower in FA than in FTC (p < 0.05, all). ROC curve analysis revealed that ADC25 resulted in the highest AUC (0.867; confidence interval, 0.616-0.980), with a cut-off value of 0.352×10-3 mm2/s. CONCLUSION: Histogram parameters from ADC maps could differentiate FTC from FA effectively in indeterminate nodules on USCNB, with ADC25 being the most promising parameter.

Improving the Grading Accuracy of Astrocytic Neoplasms Noninvasively by Combining Timing Information with Cerebral Blood Flow: A Multi-TI Arterial Spin-Labeling MR Imaging Study.

BACKGROUND AND PURPOSE: Systematic and accurate glioma grading has clinical significance. We present the utility of multi-TI arterial spin-labeling imaging and provide the bolus arrival time maps for grading astrocytomas. MATERIALS AND METHODS: Forty-three patients with astrocytomas (21 men; mean age, 51 years) were recruited. The classification abilities of conventional MR imaging features, normalized CBF value derived from multi-TI arterial spin-labeling imaging, normalized bolus arrival time, and normalized CBF derived from single-TI arterial spin-labeling were compared in patients with World Health Organization (WHO) grade II, III, and IV astrocytomas. RESULTS: The normalized CBF value derived from multi-TI arterial spin-labeling imaging was higher in patients with higher grade astrocytoma malignancies compared with patients with lower grade astrocytomas, while the normalized bolus arrival time showed the opposite tendency. The normalized CBF value derived from the multi-TI arterial spin-labeling imaging showed excellent performance with areas under the receiver operating characteristic curve of 0.813 (WHO II versus III), 0.964 (WHO II versus IV), 0.872 (WHO III versus IV), and 0.883 (low-grade-versus-high-grade gliomas). The normalized CBF value derived from single-TI arterial spin-labeling imaging could statistically differentiate the WHO II and IV groups (area under the receiver operating characteristic curve = 0.826). The normalized bolus arrival time effectively identified the WHO grades II and III with an area under the receiver operating characteristic curve of 0.836. Combining the normalized CBF value derived from multi-TI arterial spin-labeling imaging and normalized bolus arrival time improved the diagnostic accuracy from 65.10% to 72.10% compared with the normalized CBF value derived from multi-TI arterial spin-labeling imaging being applied independently. The combination of multi-TI arterial spin-labeling imaging and conventional MR imaging had the best performance, with a diagnostic accuracy of 81.40%. CONCLUSIONS: Multi-TI arterial spin-labeling imaging can evaluate perfusion dynamics by combining normalized bolus arrival time and normalized CBF values derived from multiple TIs. It is superior to single-TI arterial spin-labeling imaging and conventional MR imaging features when applied independently and can improve the diagnostic accuracy when combined with conventional MR imaging for grading astrocytomas.

Effects of ammonia exposition on glioma cells: changes in cell volume and organic osmolytes studied by diffusion-weighted and high-resolution NMR spectroscopy.

NH(4)Cl (10 mM) caused a sustained increase in the cell volume in immobilized, perfused F98 glioma cells to approx. 125% of control after 3 h, as measured by diffusion-weighted (1)H NMR spectroscopy. Concomitantly, the glutamine (Gln) concentration increased by 130%, accompanied by a marked decrease in cytosolic osmolytes, i.e. myo-inositol and taurine, determined from (1)H NMR spectra of PCA extracts. Inhibition of Gln synthetase partially prevented the increase in water content. While losses of organic osmolytes are also observed under hypotonic conditions, the rapid cell swelling is followed by the regulatory cell volume decrease (RVD), and is accompanied by decreased cytosolic Gln. We suggest that the rise in intracellular osmolarity, which is attributed to NH(4)Cl metabolism to Gln, but also to alanine (Ala), is not compensated by the release of other osmolytes, and causes cell swelling without RVD.

Water signal attenuation in diffusion-weighted 1H NMR experiments during cerebral ischemia: influence of intracellular restrictions, extracellular tortuosity, and exchange.

The "concept of restricted intracellular water diffusion at permeable boundaries", which was recently used to model diffusion-weighted 1H NMR experiments on glioma cells, was applied to measurements on the rat brain in vivo. Combined with the "concept of extracellular tortuosity", various physiological states of the brain were simulated. Hereby, a variable intracellular volume fraction, intracellular exchange time, and extracellular tortuosity factor were considered for young, adult, and ischemic rat brains. The model simulated the cytotoxic shift of extracellular water, changes in membrane permeability and tissue morphology, and was able to explain the diffusion time dependence as well as the non-monoexponentiality of the diffusion attenuation curves. Preliminary diffusion time dependent experiments on the healthy rat brain (1H NMR imaging) agreed well with the theoretical concept. Hereby, the intracellular water signal was separated from extracellular signal contributions by large diffusion weighting. It showed the characteristic of restricted diffusion as well as a signal decay due to the exchange of intracellular water across the plasma membrane. A map of the mean intracellular exchange time for water in living animal brain was determined, and the upper limit in rat brain was evaluated to 15 ms. The presented methods can be applied to correlate local differences in a map of exchange times with tissue morphology and to detect pathological deviations of the exchange time, e.g., during ischemia.

Monitoring of cell volume and water exchange time in perfused cells by diffusion-weighted 1H NMR spectroscopy.

Diffusion of intracellular water was measured in perfused cells embedded in basement membrane gel threads. F98 glioma cells, primary astrocytes, and epithelial KB cells were used and were exposed to osmotic stress, immunosuppressiva, the water channel blocker p-chloromercuriobenzenesulfonate (pCMBS), and apoptotic conditions. With diffusion-weighted 1H NMR spectroscopy changes in the intracellular signal could be monitored and quantified with single signal (ss), constant diffusion time (ct), and constant gradient strength (cg) experiments. The temporal resolution of the ss monitoring was 3.5 s with a standard deviation of 0.5% of the signal intensity and 32 s (3%) with ct monitoring, respectively. A mean intracellular residence time of water was determined with the cg experiment to about 50 ms. Changes of this exchange time from (51.9 +/- 1.0) to (59.0 +/- 1.1) ms were observed during treatment with pCMBS. The changes in the diffusion attenuated signal could be simulated analytically varying the intracellular volume fraction and exchange time by combination of restricted diffusion (Tanner model) and water exchange (Kärger model). This sensitive and noninvasive NMR method on perfused cells allows to determine changes in the intracellular volume and residence time in a simple and accurate manner. Many further applications as anoxia, volume regulation, ischemia and treatment with various pharmaceuticals are conceiveable to follow up their effect on the cell volume and the exchange time of intracellular water.

Restricted diffusion and exchange of intracellular water: theoretical modelling and diffusion time dependence of 1H NMR measurements on perfused glial cells.

Intracellular diffusion properties of water in F98 glioma cells immobilized in basement membrane gel threads, are investigated with a pulsed-field-gradient spin-echo NMR technique at diffusion times from 6 to 2000 ms and at different temperatures. In extended model calculations the concept of 'restricted intracellular diffusion at permeable boundaries' is described by a combined Tanner-Kärger formula. Signal components in a series of ct experiments (constant diffusion time) are separated due to different diffusion properties (Gaussian and restricted diffusion), and physiological as well as morphological cell parameters are extracted from the experimental data. The intracellular apparent diffusion coefficients strongly depend on the diffusion time and are up to two orders of magnitude smaller than the self diffusion constant of water. Propagation lengths are found to be in the range of 4-7 microns. Hereby intracellular signals of compartments with a characteristic diameter could be selected by an appropriate gradient strength. With cg experiments (constant gradient) a mean intracellular residence time for water is determined to be about 50 ms, and the intrinsic intracellular diffusion constant is estimated to 1 x 10(-3)mm2/s. Studying the water diffusion in glial cells provides basic understanding of the intracellular situation in brain tissue and may elucidate possible influences on the changes in the diffusion contrast during ischemic conditions.