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R G Steen

Publications and source records attributed to R G Steen.

54 records · Page 3Linked to original sources
PubMed1992

Applications of magnetic resonance spectroscopy to the investigation of neuropsychiatric disorders.

Magnetic resonance spectroscopy (MRS) can noninvasively characterize tissue composition and metabolism in vivo without the need for radioactive isotope administration. For the neuropsychiatrist interested in the functional basis of disease, MRS offers an investigative tool capable of studying a wide variety of neuropsychiatric disorders. This report provides an overview of how MRS works, current and potential clinical applications for specific psychiatric populations, and limitations of the technology.

Brain Chemistry↗
PubMed1991

31P magnetic resonance spectroscopy is sensitive to tumor hypoxia: perfusion and oxygenation of rat 9L gliosarcoma after treatment with BCNU.

The mechanism behind the relative increase in high-energy phosphates observed by MRS in many tumors following chemotherapy is poorly understood. To test the hypothesis that this metabolic activation is associated with a decrease in tumor hypoxia, tumor blood flow and oxygenation were measured in tumors that were also analyzed by MRS. 31P MR spectra were acquired with a GE 2T CSI spectrometer from subcutaneous 9L tumors in rats 4 days following treatment with BCNU (10 mg/kg) and from age-matched sham-treated control tumors. BCNU-treated tumors (n = 13) underwent a significant improvement in bioenergetic state compared to control tumors (n = 14), showing a relative increase in high-energy phosphate (Pi/phosphocreatine) (p less than 0.01), and a relative decrease in Pi (Pi/alpha nucleoside biphosphate) (p less than 0.01). Gamma camera imaging of 133Xe washout, following injection of 133Xe in saline into control and treated 9L tumors 4 days after treatment, was used to measure tumor perfusion. Sham-treated control tumors (n = 21) were perfused at a rate of 35.4 (+/- 6.4 SE) mL/100 g/min, while BCNU-treated tumors (n = 20) were perfused at a rate of 55.1 (+/- 7.5 SE) mL/100 g/min (T = 1.96; p less than 0.05). The partial pressure of oxygen (pO2), measured with a polarographic electrode was found to be significantly higher in treated 9L than in sham-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Characterization of tumor hypoxia by 31P MR spectroscopy.

Tumor hypoxia is of considerable importance to the oncologist in selecting and optimizing cancer therapy, because hypoxia can determine the effectiveness of various therapies. The relationship between tumor hypoxia and tumor bioenergetics, assessed by 31P MR spectroscopy, is examined to determine whether 31P MR spectroscopy can be clinically useful to measure or characterize tumor hypoxia. Work with experimental tumors has suggested that several different types of hypoxia may exist and that 31P MR spectroscopy cannot be used to characterize all types. Metabolic hypoxia is the level of hypoxia that results in mitochondrial impairment in cells, and it is associated with declining cellular bioenergetic status, which can be measured by enzymatic assay of adenosine triphosphate (ATP). Because 31P MR spectroscopy is sensitive to levels of ATP, it is potentially sensitive to metabolic hypoxia in vivo and may provide a rapid and noninvasive technique for characterizing metabolic hypoxia in tumors. Radiobiologic hypoxia is the level of hypoxia that results in attenuated cell death due to radiation, because radiotoxicity is directly related to tissue levels of oxygen. Radiobiologic hypoxia of tumors thus has more impact on choice of therapy, yet the relationship between metabolic hypoxia and radiobiologic hypoxia remains to be elucidated. An analysis of published data suggests that 31P MR spectroscopy is directly sensitive to metabolic hypoxia in tumors, but it is only indirectly sensitive to radiobiologic hypoxia in tumors. Therefore, 31P MR spectroscopy may be unable to quantify the cell fraction of a tumor that has radiobiologic hypoxia. However, preliminary data suggest that MR spectroscopy may prove useful for determining the effectiveness of therapeutic interventions designed to manipulate radiobiologic hypoxia in tumors or for monitoring the kinetics of tumor reoxygenation after treatment.

Animals↗
PubMed1989

Response of solid tumors to chemotherapy monitored by in vivo 31P nuclear magnetic resonance spectroscopy: a review.

In vivo 31P nuclear magnetic resonance (MR) spectroscopy has shown great promise as a tool for cancer research and the clinical management of solid tumors. It is now possible in some cases to integrate MR spectroscopy with routine MR imaging of the cancer patient, so that tissue identified as tumor on an MR image can be examined biochemically and monitored following treatment. Alterations have been observed in the phosphorus MR spectra of patient tumors after treatment, but the causes and consequences of these alterations are poorly understood. Here we review data obtained from experimental animal tumor models treated with chemotherapy in order to gain insight into the biological events reflected in MR spectroscopic changes, and to determine what information the spectra provide about the success or failure of therapeutic interventions. An attempt is made to relate these experimental findings to the cancer clinic and to analyze the contributions of MR spectroscopy to the understanding of tumor biology.

Animals↗
PubMed1989

In vivo 31P nuclear magnetic resonance spectroscopy of rat 9L gliosarcoma treated with BCNU: dose response of spectral changes.

The 9L gliosarcoma, grown subcutaneously in juvenile Fischer 344 rats, was studied by in vivo 31P NMR spectroscopy following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea. Dose-dependent increases in the proportion of high-energy phosphates were observed for doses between 10 and 36 mg/kg (from 80% of the LD10 to greater than the LD50). These doses reduced clonogenic cell survival in a dose-dependent fashion by as much as 3 log orders and resulted in up to 16 days of growth delay (to pretreatment tumor volume). Increases in high-energy phosphates (relative to Pi) in the tumor were greater at higher doses despite the higher levels of clonogenic cell killing and the substantial host systemic toxicity.

Animals↗
PubMed1989

31P NMR spectroscopic and near infrared spectrophotometric studies of effects of anesthetics on in vivo RIF-1 tumors. Relationship to tumor radiosensitivity.

Mice with subcutaneous RIF-1 tumors were anesthetized with sodium pentobarbital (PB) or ketamine plus acepromazine (KA) before acquisition of in vivo 31P nuclear magnetic resonance (NMR) spectra from tumors. The area of the inorganic phosphate resonance was significantly greater (relative to phosphomonoesters or the alpha-phosphate resonance of nucleoside triphosphate) in spectra obtained under PB anesthesia, suggesting that the hypoxic fraction of the tumor increased following PB anesthesia. In vivo near-infrared laser spectroscopy directly demonstrated that tumor oxyhemoglobin was reduced by more than 20% following PB but was not significantly affected by KA. Total hemoglobin (tumor blood volume) was reduced by 11% following PB anesthesia, but was not significantly affected by KA. Tumor growth delay induced by gamma-irradiation was shorter when tumors were irradiated under PB anesthesia than when irradiated under KA, showing that PB anesthesia had a radioprotective effect. These studies demonstrate that both the 31P NMR and near infrared methods can detect metabolic or physiological changes associated with an increase in tumor radioresistance (i.e., an increase in the radiobiological hypoxic fraction).

Acepromazine↗
PubMed1989

31P NMR spectroscopic study of bioenergetic changes in radiation-induced fibrosarcoma-1 after radiation therapy.

The effects of localized gamma-irradiation on the in vivo 31P NMR spectra of RIF-1 tumors grown subcutaneously in C3H/HeN mice have been examined before and during the week after treatment. Increases in the ratio of phosphocreatine (PCr) to inorganic phosphate (Pi) and in tumor pH, and decreases in the ratio of Pi to the beta phosphorus resonance of the nucleotide triphosphates (beta NTP) were observed in irradiated tumors. The time course of changes in the 31P spectrum following treatment was the opposite of the pattern during untreated growth, and the magnitude and duration of the changes increased with increasing radiation dose, decreasing clonogenic cell survival and increasing growth delay. To examine the possibility that nontherapeutic systemic effects of the tumor irradiation were responsible for the changes observed, a number of animals bearing two tumors were examined. One tumor on each mouse was selectively irradiated. Changes in tumor volume, Pi/beta NTP, PCr/Pi, the ratio of phosphomonoesters to beta NTP, and tumor pH were all significantly different in the treated compared to the untreated tumor on each animal, indicating that these changes in 31P NMR spectra were a response to radiation therapy and not a systemic response to radiation toxicity.

Animals↗
PubMed1988

Response of radiation-induced fibrosarcoma-1 in mice to cyclophosphamide monitored by in vivo 31P nuclear magnetic resonance spectroscopy.

In vivo 31P nuclear magnetic resonance spectroscopy has been used to examine the RIF-1 fibrosarcoma in mice during untreated growth and following chemotherapy with cyclophosphamide. Levels of inorganic phosphate increase relative to phosphocreatine or nucleoside triphosphates during early untreated growth. After the tumor reaches a volume of approximately 1 g, no further decrease in energy level is observed. Following treatment with cyclophosphamide, tumor phosphorus metabolite ratios and pH are significantly altered, compared to untreated age-matched controls. During the growth delay period following chemotherapy there is a significant reduction in the ratio of inorganic phosphate to other phosphate metabolites, compared to age-matched controls. In addition, a more alkaline pH is observed in the tumors of treated animals. When the growth delay period ends, nuclear magnetic resonance spectra return to pretreatment patterns. The magnitude of the differences in 31P nuclear magnetic resonance spectral parameters between treated animals and untreated controls is dose dependent. However, doses of cyclophosphamide above 200 mg/kg do not result in earlier spectroscopic alterations, nor in larger effects by Day 3 after treatment, even though clonogenic cell killing and growth delay are greater at these higher doses.

Animals↗
PubMed1988

In vivo 31P nuclear magnetic resonance spectroscopy of subcutaneous 9L gliosarcoma: effects of tumor growth and treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea on tumor bioenergetics and histology.

In vivo 31P nuclear magnetic resonance spectroscopy was used to examine the bioenergetics of the rat 9L gliosarcoma during untreated growth and in response to chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea. Tumor growth was associated with a decline in the phosphocreatine and nucleoside triphosphate resonances, consistent with an increase in tumor hypoxia during untreated growth. Following chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (10 mg/kg), tumor levels of phosphocreatine and nucleoside triphosphate rebounded while the level of inorganic phosphate in the tumor declined. Histological comparison of treated and untreated tumor sections 4 days posttreatment showed that the treated tumor had a lower proportion of necrotic cells, a higher proportion of viable cells, and a 5-fold higher level of interstitial space than the control tumor.

Animals↗
PubMedDate not supplied

Discrete signal processing of dynamic contrast-enhanced MR imaging: statistical validation and preliminary clinical application.

A high-resolution image-based method was developed to analyze dynamic contrast agent-enhanced magnetic resonance images quantitatively. This method determines the initial rate of contrast agent accumulation, the delayed rate of accumulation, and the maximum enhancement in each pixel. These three parameters allow characterization of the dynamic signal features. Simulated noisy test sets of dynamic enhancement curves have shown this method to yield a fast and accurate characterization of the dynamic signal. Clinical examples of both qualitative image parameter maps and quantitative statistical analysis of the parameter distributions demonstrated the quality and potential of the technique. The technique is designed to yield imaging and quantitative information on contrast agent accumulation that can be useful in detecting residual tumor and evaluating response to therapy, while requiring less than 7 minutes of imaging time and 5 minutes of processing time per study.

Adult↗
PubMedDate not supplied

Precise and accurate measurement of proton T1 in human brain in vivo: validation and preliminary clinical application.

Precise and accurate inversion-recovery (PAIR) magnetic resonance (MR) measurements of T1 were obtained in eight brain regions and cerebrospinal fluid of 26 healthy volunteers. Accuracy of the technique was assessed by measuring T1 in small fluid volumes with the PAIR technique and with two independent spectroscopic techniques. The mean difference between T1 measured with PAIR and with the two spectroscopic techniques was 3.1% +/- 1.3. The precision (reproducibility) of measurements with the PAIR technique was excellent. The coefficient of variation (CV) across 16 measurements in a head phantom was 2.0%, compared with a CV of 2.7% across 45 separate measurements in a single subject. The within-subject CV was 1.8% +/- 0.6 in white matter and 1.4% +/- 1.0 in basal ganglia. The between-subject CV in 26 healthy volunteers was 3.6% +/- 0.6 in white matter and 4.1% +/- 1.9 in basal ganglia. Comparison between a patient with an active recurrent brain tumor and an age-matched patient with an inactive brain tumor showed that T1 was significantly elevated throughout the brain of the active-tumor patient, especially in white matter tracts, even though no tumor or edema was detected in the white matter on standard MR images. Comparisons between five brain tumor patients and four healthy volunteers of similar age showed that T1 was significantly and substantially elevated throughout the white matter tracts and in the caudate nucleus, putamen, and thalamus. These results are consistent with the hypothesis that white matter tracts are selectively vulnerable to edema and that T1 increases in white matter are a sensitive indicator of patient status or tumor aggressiveness.

Adolescent↗
PubMedDate not supplied

Age-related changes in proton T1 values of normal human brain.

To determine whether there were age-related changes in the brain tissue of 55 healthy adult volunteers (29 men, 26 women; 18-72 years old) without known brain abnormalities, a standard inversion-recovery technique was optimized for precise and accurate T1 measurement within the constraints of a 15-minute examination. Measurements of water proton T1 were obtained in eight brain regions. T1 increased with age in the genu (P < .001) (analysis of variance), frontal white matter (P < .05), occipital white matter (P < .05), putamen (P < .001), and thalamus (P << .001). A significant decrease in T1 with age was found in cortical gray matter (P < .05). Thus, age-related changes in T1 are present in a healthy population, even if extremes of age are excluded, suggesting that T1 values generally increase with age. However, increases in T1 were also observed in the genu, putamen, and thalamus of a substantial fraction of volunteers less than 35 years old. Aging healthy persons can show subtle, nonsymptomatic brain changes, suggesting that brain aging is associated with occult processes that can begin at a relatively early age.

Adolescent↗
PubMedDate not supplied

Quantitative MR imaging of children with sickle cell disease: striking T1 elevation in the thalamus.

Nineteen patients with sickle cell disease (SCD) were examined with conventional MR imaging (cMRI), including T1- and T2-weighted sequences and MR angiography (MRA). qMRI mapping of T1 was also done using a precise and accurate inversion-recovery (PAIR) technique optimized and validated previously. In addition, 21 healthy African-American control subjects had the qMRI examination. Nonparametric Kruskal-Wallis analysis of variance of control subjects, of SCD patients without stroke, and of SCD patients with stroke showed that T1 increased with disease severity in the thalamus, frontal white matter, genu, and occipital white matter. T1 was significantly longer in SCD patients without stroke (n = 13) than in control subjects (n = 21) in the thalamus and frontal white matter. In addition, T1 values were significantly longer in SCD patients with stroke than in patients without stroke in the genu and frontal white matter. Abnormality of the thalamus was identified by qMRI in a substantial fraction of patients read as normal by both cMRI and MRA, suggesting that it may be possible to use T1 elevation to identify a subset of patients with SCD who are at elevated risk for stroke.

Adolescent↗
PubMedDate not supplied

Statistical error mapping for reliable quantitative T1 imaging.

We developed a statistically based error image for rapid appreciation of unreliable regions in quantitative water proton T1 images. The chi-squared error and co-efficient of variation of the fitted parameter were used to estimate uncertainties in the goodness-of-fit to mono-exponential T1 relaxation and the reliability of the calculated T1, respectively, for each pixel. Errors exceeding a statistical threshold based on a .1 acceptance criterion were displayed as a color-coded overlay on the T1 image. Error maps of quantitative T1 images from 31 healthy volunteers showed a characteristic error structure; few pixels within the parenchyma had excessive errors. Clinical cases with stroke and sickle cell disease showed deviations from the normal pattern in the spatial distribution and magnitude of chi-squared errors. Disease states may deviate from mono-exponential T1 relaxation more than normal brain does. The color-coded error map is a valuable tool for investigators using quantitative MR imaging to determine tissue relaxation parameters.

Adult↗
PubMedDate not supplied

Fat-saturated contrast-enhanced T1-weighted MRI in evaluation of osteosarcoma and Ewing sarcoma.

To assess contrast-enhanced (C+), fat-saturated (FatSat), T1-weighted (T1W) imaging in the characterization of the soft tissue mass associated with primary bone tumors, we compared it with T2-weighted (T2W) imaging in patients with osteosarcoma (n = 36) and Ewing sarcoma family of tumors (Ewing sarcoma; n = 11). Periosseous tumor compared with normal muscle had greater contrast-to-noise ratio (CNR) on the FatSat T1W C+ image than on T2W for 81% (38/47; P < .0001) of patients. The CNR of periosseous tumor compared with subcutaneous fat was greater on FatSat T1W C+ for 98% (46/47; P < .0001). Radiologists found it easier to evaluate neurovascular bundle proximity to tumor with FatSat T1W C+ images than with T2W for 64% of patients (30/47; P < .0001). They judged FatSat T1W C+ superior to T2W for periosseous tumor conspicuity and visualization of soft tissue necrosis in 62% (29/47; P < .0001). In patients with osteosarcoma or Ewing sarcoma, FatSat T1W C+ imaging may replace T2W imaging for soft tissue mass evaluation, especially if contrast is being used for dynamic enhancement.

Adolescent↗
PubMedDate not supplied

Quantitative MRI of the brain in children with sickle cell disease reveals abnormalities unseen by conventional MRI.

Conventional MRI (cMRI) has shown that brain abnormalities without clinical stroke can manifest in patients with sickle cell disease (SCD). We used quantitative MRI (qMRI) and psychometric testing to determine whether brain abnormalities can also be present in patients with SCD who appear normal on cMRI. Patients 4 years of age and older with no clinical evidence of stroke were stratified by cMRI as normal (n = 17) or abnormal (n = 13). Spin-lattice relaxation time (T1) of gray and white matter structures was measured by the precise and accurate inversion recovery (PAIR) qMRI method. Patient cognitive ability was assessed with a standard psychometric instrument (WISC-III or WISC-R). In all 30 patients with SCD, qMRI T1 was lower than in 24 age- and race-matched controls, in cortical gray matter (P < .0006) and caudate (P < .0009), as well as in the ratio of gray-to-white matter T1 (P < .008). In the 17 patients who were shown to be normal by cMRI, qMRI T1 was still lower than in controls, in both cortical gray matter (P < .02) and caudate (P < .004). Histograms of voxel T1 show that the proportion of voxels with T1 values intermediate between gray and white matter (ie, consistent with encephalomalacia) was 9% higher than controls in patients shown to be normal by cMRI (P < .05) and 15% higher than controls in patients shown to be abnormal by cMRI (P < .0005). The full scale intelligence quotient (FSIQ) of all patients with SCD was 75, compared to the FSIQ of 88 in a historical control group of patient siblings (P < .001). The FSIQ of patients shown to be normal by cMRI was 79, significantly lower than the FSIQ of patient siblings (P < .04). The FSIQ of 71 in patients shown to be abnormal by cMRI was significantly lower than both the patient siblings (P < .005) and the patients shown to be normal by cMRI (P < .04). Patients shown to be abnormal by cMRI scored lower than patients shown to be normal by cMRI, specifically on the subtests of vocabulary (P = .003) and information (P = .03). Cognitive impairment is thus significant, even in patients with SCD who were shown to be normal by cMRI, suggesting that cMRI may be insensitive to subtle neurologic damage that can be detected by qMRI. Because cognitive impairment can occur in children normal by cMRI, our findings imply that prophylactic therapy may be needed earlier in the course of SCD to mitigate neurologic damage.

Adolescent↗