Biomedical subjects

Paul S Tofts

Publications and source records attributed to Paul S Tofts.

16 recordsLinked to original sources

PubMed2007

Quantitative analysis of whole-tumor Gd enhancement histograms predicts malignant transformation in low-grade gliomas.

PURPOSE: To quantify subtle gadolinium (Gd) enhancement (signal increase) in whole-tumor histograms and optimize their ability to predict subsequent malignant transformation in low-grade gliomas (LGGs). MATERIALS AND METHODS: We analyzed histograms from 21 adult subjects with LGGs (eight nontransformers and 13 transformers) who had been imaged every six months for periods of two to five years. Before transformation these tumors were reported as radiologically non-enhancing. Imaging included a T(1)-weighted volume sequence before and after a double dose of Gd-DTPA contrast agent. Image data sets were spatially registered and subtracted to obtain maps of percent enhancement (%E). Tumor outlines were defined on fluid-attenuated inversion recovery (FLAIR) images, and the volumes were calculated. Histogram tails were analyzed to obtain the volume (mL) of subtly enhancing tissue (%E > 10%). RESULTS: Baseline enhancing volumes were higher for Ts than for NTs (P < 0.005). Kaplan-Meier survival curves for a threshold of 4 mL showed clear differences at five years (P < 0.04). Pretransformation examinations predicted transformation (corrected threshold = 3.0 mL, P = 0.011). CONCLUSION: Clear histogram differences at presentation suggest that the process of transformation starts very early. It is now possible to identify individuals at high risk for transformation at baseline by quantifying the volume of subtly enhancing tumor tissue, and such findings could have an impact on patient management.

Adult↗

PubMed2007

Apparent diffusion coefficient histograms may predict low-grade glioma subtype.

The subtypes of glioma are known to have different prognosis and response to treatment. The purpose of this work was to investigate whether apparent diffusion coefficient (ADC) histograms of untreated low-grade astrocytomas and oligodendrogliomas exhibit different characteristics due to their biological differences, and whether a diagnosis of tumour subtype can be made at presentation using the histogram alone, which, if possible, would have an impact on clinical practise. Fifteen patients with astrocytoma (AC) [11 male (mean age +/- standard deviation) 40 +/- 11 years], nine with oligodendroglioma (OD) (four male, 45 +/- 13 years) and three with oligoastrocytoma (OA) (two male, 60 +/- 11 years) were recruited and diffusion-weighted images (b = 0 and 1000 s mm(-2)) were acquired every 6 months to date or until malignant transformation. Whole tumour ADC histograms were calculated, a multiple discriminant analysis was performed and quantitative morphological parameters extracted, the AC and OD subtypes were then compared using Student's unpaired t-test. Classification of the histograms was also performed. ODs had significantly lower group ADC values than ACs and up to 83% of the subjects could be correctly classified into the OD and AC groups by reference to the histogram. The group differences were most significant for the multiple discriminant analysis (p = 1 x 10(-5)) and at the 10th centile point [AC = 1170 +/- 170, OD = (1030 +/- 80) x 10(-6) mm(2) s(-1)] (p = 0.01). ODs have a lower ADC than ACs with differences throughout the histogram. Both tumour types show similar intra-tumour heterogeneity, as seen from the equal group peak heights, but ACs shows more intra-group heterogeneity. ADC histogram analysis may aid non-invasive sub-classification of low-grade glioma histological subtypes.

Adult↗

PubMed2006

Principal component and linear discriminant analysis of T1 histograms of white and grey matter in multiple sclerosis.

Twenty-three relapsing remitting multiple sclerosis (RRMS) patients and 14 controls were imaged to produce normal-appearing white and grey matter T1 histograms. These were used to assess whether histogram measures from principal component analysis (PCA) and linear discriminant analysis (LDA) out-perform traditional histogram metrics in classification of T1 histograms into control and RRMS subject groups and in correlation with the expanded disability status score (EDSS). The histograms were classified into one of two groups using a leave-one-out analysis. In addition, the patients were scanned serially, and the calculated parameters correlated with the EDSS. The classification results showed that the more complex techniques were at least as good at classifying the subjects as histogram mean, peak height and peak location, with PCA/LDA having success rates of 76% for white matter and 68%/65% for grey matter. No significant correlations were found with EDSS for any histogram parameter. These results indicate that there is much information contained within the grey matter as well as the white matter histograms. Although in these histograms PCA and LDA did not add greatly to the discriminatory power of traditional histogram parameters, they provide marginally better performance, while relying only on data-driven feature selection.

Brain↗

PubMed2005

A simple correction for B1 field errors in magnetization transfer ratio measurements.

B1 errors are a problem in magnetization transfer ratio (MTR) measurements because the MTR value is dependent on the amplitude of the magnetization transfer (MT) pulse. B1 errors can arise from radiofrequency (RF) nonuniformity (caused by the RF coil, or skin effect and dielectric resonance in the subject's head) and also from inaccurate setting of the transmitter output when compensating for varying amounts of loading of the RF coil. B1 errors, and hence MTR errors, may be up to 5-10%, a large source of error in quantitative MR measurements. Radiofrequency nonuniformity may cause MTR histograms to be broadened. The dependence of MTR on B1 was modeled using binary spin bath theory, with a continuous wave (CW) approximation. For B1 reductions of up to 20%, normalized plots for different brain tissue types could be approximated by a single line, indicating that a systematic correction could be applied to MTR measurements with a known B1 error, regardless of tissue type. On a 1.5-T scanner with a birdcage coil, MTR was measured in 18 tissue types in five controls. The MT pulse amplitude was reduced in steps from its nominal value by up to 20%. Averaging data over all controls and tissue types resulted in a line fitting mtr(normalized)=0.812b(1normalized)+0.193, where mtr(normalized) is the normalized value of MTR (relative to its value at the nominal B1) and b(1normalized) is the normalized value of B1 (relative to its nominal value). For a 20% reduction in MT pulse amplitude (i.e., b(1normalized)=0.80), the mean MTR value for the 18 tissue types was 7.0 percent units (pu) below the correct value. After correction using the single equation above for all tissue types, all MTR values were within 1.5 pu of their correct value [root mean square (rms) error=0.7 pu]. Magnetization transfer ratio values tended to be slightly overcorrected because the simple linear correction scheme is only an approximation to the true MTR dependence on B1. A B1 field mapping technique was implemented, based on the double angle method (DAM), with fast spin-echo (FSE) readout, and TR=15 s; this took a total of 6 min of imaging time. This was used to quantify B(1) errors and correct MTR maps and histograms. However, the cerebrospinal fluid (CSF) T1 is very long (approximately 4.2 s); thus, to achieve complete longitudinal relaxation (a requirement of the DAM B1 mapping method), an increase in TR and, hence, acquisition time would be required. In general, however, we are not interested in calculating the B1 in the CSF, although it is important that the B1 is determined in partial volume voxels around the CSF. Using our birdcage head coil, whole-brain B1 histograms were found to have full-width half maximums (FWHMs) ranging from just 6.8% to 11.5% of the nominal B1 value. The FSE DAM B1 field mapping technique was shown to be robust, although a longer TR time may be desirable to ensure complete elimination of CSF partial volume errors. The procedure can be applied on any scanner where the Euro-MT sequence is available, or alternatively, where the amplitude of B1 or of the MT pulse can be manually reduced in order to perform this type of "calibration" experiment for the particular MTR sequence used. The MTR is known to be highly dependent on the parameters of the sequence used, in particular, the MT pulse shape, flip angle, duration, and offset frequency, and the repetition time TR' between successive MT pulses. Therefore, correction schemes will differ for different MTR sequences, and new data sets would be required to calculate these different correction schemes.

Algorithms↗

PubMed2005

Unbiased segmentation of diffusion-weighted magnetic resonance images of the brain using iterative clustering.

Segmentation of diffusion-weighted echo-planar imaging (DW-EPI) is challenging because of concerns regarding spatial resolution and distortion. Methods commonly used require manual input and often need thresholding measures to segment white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF). This may introduce operator bias and misclassification error. When comparing patients with a diffuse disease process-such as multiple sclerosis (MS)--with healthy controls, although information from all images may be biased due to disease effect, this is more so if the data set employed to perform segmentation is also used as a measured outcome for the study, for example, fractional anisotropy maps. Presented in this work is an unbiased method for segmenting DW-EPI data sets using the b=0 and single-shot inversion recovery EPI into WM, GM and CSF. The method employs an iterative clustering technique to account for partial volume effects and signal variation caused by radiofrequency inhomogeneity. The technique is evaluated with both real and synthetic brain data and results compared with statistical parametric mapping (SPM02). With synthetic brain data, where a gold standard of segmentation exists, the presented method showed less misclassification compared to SPM02. The unbiased method proposed may provide a more accurate methodology of segmentation in the analysis of DWI-EPI images in conditions such as MS.

Algorithms↗

PubMed2005

Three-dimensional quantitative magnetisation transfer imaging of the human brain.

Quantitative magnetisation transfer (MT) analysis is based on a two-pool model of magnetisation transfer and allows important physical properties of the two proton pools to be assessed. A good signal-to-noise ratio (SNR) for the measured signal is essential in order to estimate reliably the parameters from a small number of samples, thus prompting the use of a sequence with high SNR, such as a three-dimensional spoiled gradient acquisition. Here, we show how full brain coverage can be accomplished efficiently, using a three-dimensional acquisition, in a clinically acceptable time, and without the use of large numbers of slice-selective radio-frequency pulses which could otherwise confound analysis. This acquisition was first compared in post mortem human brain tissue to established two-dimensional acquisition protocols with differing SNR levels and then used to collect data from six healthy subjects. Image data were fitted using the two pool model and showed negligible residual deviations. Quantitative results were assessed in several brain locations. Results were consistent with previous single-slice data, and parametric maps were of good quality. Further investigations are needed to interpret the regional variation of quantitative MT quantities.

Adult↗

PubMed2005

Assessment and correction of B1-induced errors in magnetization transfer ratio measurements.

The magnetization transfer ratio (MTR) is strongly related to the field strength (B(1)) of the saturation pulse. B(1) variations therefore can result in significant MTR variations and can affect histogram analysis, particularly if data from a large volume of interest are included. A multicenter study was performed to determine the typical range of B(1) errors and the corresponding MTR variations in brain tissue of healthy volunteers. Seven subjects were included at each center resulting in a total cohort of 28 subjects. Additionally, numerical simulations were done to study this relationship more generally for pulsed saturation. It could be demonstrated, both theoretically and empirically, that for typical B(1) errors there is a linear relationship between B(1) error and the corresponding MTR change. In addition, for proton density-weighted sequences, this relationship seems to be largely independent of the underlying relaxation properties. Mean B(1) errors in the entire brain were typically in the range between -3% and -7%. Due to different coil characteristics, significant MTR differences between different scanners and sites were observed. Using a simple correction scheme that is based on a linear regression analysis between MTR and B(1) data it was possible to reduce the intersubject variation by approximately 50%. Furthermore, interscanner variation could be reduced such that no significant differences between scanners could be detected. The correction scheme may be useful when investigating MTR as an outcome measure in single or multicenter studies.

Adult↗

PubMed2005

Dynamic contrast enhanced MRI in patients with diabetic macular edema: initial results.

To assess the ability of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to detect blood retinal barrier (BRB) damage in patients with diabetic macular edema (DME). DCE-MRI with 0.1 mmol Gd-DTPA was used to measure BRB permeability in 10 healthy and visually normal subjects and eight patients with DME, including five patients with non-clinically significant (NCS) DME and three patients with clinically significant (CS) DME. For each subject, the enhancement of the MRI signal intensity in the pre-macular vitreous was measured as a function of time following contrast injection. A linear regression analysis was performed on each subject and the slopes of the contrast enhancement functions were compared. The DCE-MRI procedure was well tolerated by all 18 subjects. However, in four subjects, excessive eye movements resulted in spurious results. Consequently, 78% (14/18) of the subjects provided usable data. The mean slope of the control group was not significantly (p>0.05) different from zero (i.e. signal intensity in the pre-macular vitreous space was constant as a function of time post-contrast injection). For the diabetic patients, the average slope of the contrast enhancement function was significantly greater than in the control group (p<0.01). Furthermore, for both diabetic sub-groups, the average slopes were greater (p<0.05) than that for the control group but not significantly (p>0.05) different from each other. This 'proof of concept' study demonstrated that DCE-MRI detects passive leakage through the BRB in diabetic patients with either NCS or CS macular edema. In future studies, DCE-MRI may be useful for early quantitative evaluation of drug treatment effects in patients with DME.

Adult↗

PubMed2004

Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects.

Before meaningful conclusions can be drawn from clinical measures of cerebral blood perfusion, the precision of the measurement must be determined and set in the context of inter- and intrasubject sources of variability. This work establishes the reproducibility of perfusion measurements using the noninvasive MRI technique of continuous arterial spin labeling (CASL). Perfusion was measured in 34 healthy normal subjects. Intersubject variability was assessed, and age and gender contributions were estimated. Intersubject variation was found to be large, with up to 100% perfusion difference for subjects of the same age and gender. Repeated measurements in one subject showed that perfusion remains remarkably stable in the short term when compared with intersubject variation and the large capacity for perfusion change in the brain. A significant decrease in the ratio of gray-matter to white-matter perfusion was found with increasing age (0.79% per year (P < 0.0005)). This appears to be due mainly to a reduction in gray-matter perfusion, which was found to decrease by 0.45% per year (P = 0.04). Regional analysis suggested that the gray-matter age-related changes were predominantly localized in the frontal cortex. Whole-brain perfusion was 13% higher (P = 0.02) in females compared to males.

Adult↗

PubMed2004

Measuring blood volume and vascular transfer constant from dynamic, T(2)*-weighted contrast-enhanced MRI.

Dynamic, contrast-enhanced MRI (deMRI) is increasingly being used to evaluate cerebral microcirculation. There are two different approaches for analyzing deMRI data. Intravascular indicator dilution theory has been used to estimate blood volume (and perfusion), usually from T(2)- or T(2) (*)-weighted images of the first pass of the bolus. However, the theory assumes that the tracer (i.e., contrast agent) remains intravascular, which is often not the case when the blood-brain barrier (BBB) is damaged. Furthermore, the method provides no information on the vascular transfer constant. Pharmacokinetic modeling analyses of T(1)-weighted images after first pass do give values of the vascular transfer constant and the volume of the extravascular, extracellular space (EES), but they generally are unable to give estimates of blood volume. In this study we apply pharmacokinetic modeling to dynamic T(2) (*)-weighted imaging of the first pass of a tracer bolus. This method, which we call first-pass pharmacokinetic modeling (FPPM), gives an estimate of the blood volume, vascular transfer constant, and EES volume. The method was applied to a group of 26 patients with surgically proven tumors (10 glioblastomas multiforme (GBMs), six lymphomas, and 10 meningiomas). The measurements of the blood volume and transfer constant were consistent with the known physiology of these tumors.

Blood Volume↗

PubMed2003

Reproducibility of brain ADC histograms.

The aim of this study was to assess the effect of differences in acquisition technique on whole-brain apparent diffusion coefficient (ADC) histogram parameters, as well as to assess scan-rescan reproducibility. Diffusion-weighted imaging (DWI) was performed in 7 healthy subjects with b-values 0-800, 0-1000, and 0-1500 s/mm(2) and fluid-attenuated inversion recovery (FLAIR) DWI with b-values 0-1000 s/mm(2). All sequences were repeated with and without repositioning. The peak location, peak height, and mean ADC of the ADC histograms and mean ADC of a region of interest (ROI) in the white matter were compared using paired-sample t tests. Scan-rescan reproducibility was assessed using paired-sample t tests, and repeatability coefficients were reported. With increasing maximum b-values, ADC histograms shifted to lower values, with an increase in peak height ( p<0.01). With FLAIR DWI, the ADC histogram shifted to lower values with a significantly higher, narrower peak ( p<0.01), although the ROI mean ADC showed no significant differences. For scan-rescan reproducibility, no significant differences were observed. Different DWI pulse sequences give rise to different ADC histograms. With a given pulse sequence, however, ADC histogram analysis is a robust and reproducible technique. Using FLAIR DWI, the partial-voluming effect of cerebrospinal fluid, and thus its confounding effect on histogram analyses, can be reduced.

Adult↗

PubMed2003

Removing spikes caused by quantization noise from high-resolution histograms.

A novel method is presented for the removal of spikes, caused by the division of two series of integers, from high-resolution histograms. When two series of integers are divided the results take the form of a nonuniform distribution. Such a division is often used in medical imaging, due to the storage of most images as integers. An example of this is the division of the saturated and unsaturated signal intensities to obtain a magnetization transfer ratio. Histograms produced using these methods often contain spikes relating to the nonuniform distribution mentioned above. These spikes can have serious implications for certain histogram characteristics. Most commonly, peak height and location can be seriously distorted by these spikes, which have predictable locations. These spikes can be removed by the addition of uniformly distributed noise to the integer signal intensities before division.

Magnetic Resonance Imaging↗

PubMed2003

Osteogenic and Ewing sarcomas: estimation of necrotic fraction during induction chemotherapy with dynamic contrast-enhanced MR imaging.

Dynamic contrast material-enhanced magnetic resonance (MR) images of primary osteogenic sarcoma (n = 19) and Ewing sarcoma (n = 10) were reviewed in 29 patients undergoing induction chemotherapy before surgery. Histogram distributions containing the initial slope and pharmacokinetic model parameters from individual voxels within each tumor were fitted for each patient. The histogram analysis of initial slope from the tumor correlated well with percentage necrosis as determined at pathologic examination (r = 0.60, P <.001), as did a two-compartment pharmacokinetic model (r = 0.64, P <.001). Both methods predicted tumors with clinically important degrees of necrosis (ie, > or =90%) in a large majority of cases. The ability to determine response to induction chemotherapy by means of noninvasive monitoring of necrotic fraction with perfusion MR imaging methods may provide useful prognostic information and help surgical planning.

Adolescent↗

PubMed2002

ADC mapping of the human optic nerve: increased resolution, coverage, and reliability with CSF-suppressed ZOOM-EPI.

The mean apparent diffusion coefficient (ADC) of the human optic nerve (ON) has been quantified in vivo, and mean ADC maps are shown along the complete length of the nerve from the globe to the optic chiasm. The mean ADC, over the whole nerve, is shown to be 1058 x 10(-6) mm(2) s(-1) (standard deviation (SD), over nine 3-mm slices, 101x10(-6) mm(2) s(-1); range (833-1178)x10(-6) mm(2) s(-1)). The robustness of the method relies on acquisition of high-resolution coronal images of the ON using the ZOOM-EPI technique, which makes use of a shortened echo train length for increased resolution with decreased susceptibility-induced distortions. Suppression of the cerebrospinal fluid (CSF) and fat signals from tissues that surround the ON also helps successful identification and delineation of the nerve. Averaging of magnitude images is used to compensate for the inherently low signal-to-noise ratio (SNR) of the acquired images; the effects of the Rayleigh distributed noise in such images are allowed for during ADC calculations.

Cerebrospinal Fluid↗

PubMed2002

Improved accuracy of human cerebral blood perfusion measurements using arterial spin labeling: accounting for capillary water permeability.

A two-compartment exchange model for perfusion quantification using arterial spin labeling (ASL) is presented, which corrects for the assumption that the capillary wall has infinite permeability to water. The model incorporates an extravascular and a blood compartment with the permeability surface area product (PS) of the capillary wall characterizing the passage of water between the compartments. The new model predicts that labeled spins spend longer in the blood compartment before exchange. This makes an accurate blood T(1) measurement crucial for perfusion quantification; conversely, the tissue T(1) measurement is less important and may be unnecessary for pulsed ASL experiments. The model gives up to 62% reduction in perfusion estimate for human imaging at 1.5T compared to the single compartment model. For typical human perfusion rates at 1.5T it can be assumed that the venous outflow signal is negligible. This simplifies the solution, introducing only one more parameter than the single compartment model, PS/v(bw), where v(bw) is the fractional blood water volume per unit volume of tissue. The simplified model produces an improved fit to continuous ASL data collected at varying delay time. The fitting yields reasonable values for perfusion and PS/v(bw).

Capillary Permeability↗

PubMed2002

Systemic lupus erythematosus: diagnostic application of magnetization transfer ratio histograms in patients with neuropsychiatric symptoms--initial results.

PURPOSE: To explore the diagnostic potential of magnetization transfer ratio (MTR) histogram analysis in patients with neuropsychiatric systemic lupus erythematosus (SLE) by using multivariate discriminant analysis (MDA). MATERIALS AND METHODS: Volumetric magnetization transfer imaging was performed in nine patients with active non-thromboembolic, neuropsychiatric SLE, 10 patients with SLE who had had neuropsychiatric SLE previously, 10 patients with SLE but no history of neuropsychiatric SLE, 10 patients with inactive multiple sclerosis, and 10 healthy control subjects. For each subject, an MTR histogram of the whole brain was generated, and an MDA score was produced for each histogram. Each patient was assigned to a clinical subgroup on the basis of these MDA scores. For assignment, binary comparisons between subgroups were made. The accuracy of this classification method was assessed and compared with that of conventional MTR histogram analysis. RESULTS: With MDA, the success rate of binary classification was 60%-100%, depending on which two groups were compared. When the different clinical subgroups were separated, MDA parameters were always better than conventional MTR histogram parameters, with P values ranging from.05 to less than 1 x 10(-6) of those attained with the best conventional parameter. CONCLUSION: With MDA, MTR histograms of brain tissue may provide diagnostic information for individual patients in the clinical context of SLE.

Adult↗