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Biomedical subjects

R Damadian

Publications and source records attributed to R Damadian.

At least 19 recordsLinked to original sources

Low paramagnetic-ion content in cancer cells: its significance in cancer detection by magnetic resonance imaging.

In previous publications, one of us demonstrated that variation in paramagnetic-ion contents is a major contributing factor to the different NMR relaxation times, T1 and T2, of water protons among normal mouse tissues; and between normal tissues and cancer cells. The nature of the paramagnetic ions involved was not determined. In the present communication, we report results of analysis of the contents of three biologically prominent paramagnetic ions (manganese, iron and copper) in 9 normal mouse tissues (brain, heart, small intestine, kidney, liver, lung, voluntary muscle, spleen and stomach); one strain of rat cancer cells (As-30, rat hepatoma); and 6 strains of mouse cancer cells (Ehrlich mammary adenocarcinoma, LSA lymphoma, Krebs carcinoma of the inguinal region; sarcoma 180; Klein TA3 mammary adenocarcinoma; P815 mast cell leukemia). Our data indicate that manganese and iron are by far the two most important paramagnetic ions contributing to the diversity of NMR relaxation times. The average manganese content of all the normal mouse tissues studied (29.6 +/- 4.99 mu mole/kg) is 24 times higher than the average manganese contents of all the cancer cells studied (1.22 +/- 0.27 mu moles/kg) and there is essentially no overlap between the two groups of data. The average iron content of the normal mouse tissues (281.6 +/- 51.2 mumoles/kg) is 4 times the average in cancer cells (66.7 +/- 7.74 mumoles/kg) but there is some overlap here. The observed differences in both the manganese and iron contents are statistically highly significant, with P's below 0.0001. The copper contents of the cancer cells is lower than the average of normal mouse tissues but only by some 20%. The difference is statistically insignificant at the 0.05 level but significant at the 0.2 level.

Animals

Field focusing n.m.r. (FONAR) and the formation of chemical images in man.

The first proposals for n.m.r. scanning in medical diagnosis was made by Damadian (1971a; 1972) and were followed by Lauterbur (1973). Damadian's method of scanning used the principle that the forced precessions of a nuclear magnetization under radio frequency (r.f.) driving field specify the conditions for obtaining spatial resolution of the signal producing domains of a nuclear resonance sample. Sufficient coupling of the nuclear spins to the radiation field to produce a signal detectable by r.f. spectroscopy requires that the stringent Bohr frequency condition, hv = microH0/I, be met. It became possible to construct, with the aid of direct current auxiliary coils, a small volume, called the resonance aperture, inside the applied static field of the magnetic resonance experiment. The correct value of H0 for the applied frequency is restricted to this aperture. The technique (Damadian 1972) was developed to provide a method for non-surgically detecting chemical abnormalities in the diseased organs of patients (Damadian 1971a). The first n.m.r. scans of normal patients and of those with malignant disease are discussed.

Animals

Pulsed nuclear magnetic resonance of potassium (39K) of whole body live and dead newborn mice. Double oscillation frequencies in T1 decay curves.

Pulsed nuclear magnetic resonance relaxation curves (T2 and T1) of potassium (39K) have been measured in detail on whole body newborn mice when alive, and on the same mice after death. The T2 curves are simple exponential with respect to time, but are shorter than for 39K in simple solutions. The T1 curves are not exponential decays, but show large oscillations that may be described approximately as the sum of two separate sine waves of different frequencies. Large T1 oscillations of complex waveform were previously observed by us with 39K in cancer tissues. Gyroscopic motion of adsorbed magnetoelectric dipoles is proposed as a possible physical mechanism accounting for the experimental observations.

Animals

NMR in cancer. X. A malignancy index to discriminate normal and cancerous tissue.

Proton nuclear magnetic resonance relaxation parameters (T1, T2, T1p) were measured on 84 normal and malignant samples of colon, lung and breast tissue at 22.5 MHz. The purpose of this study was to evaluate the ability of NMR measurements to discriminate between normal and malignant tissue. By combining T1 and T2 into a normalized NMR malignancy index, it was possible to discriminate malignant and normal tissue in all 36 colon samples, 22 out of 23 breast samples, and 26 out of 29 lung cases. Furthermore, histologically normal tissue adjacent to malignant colonic tissue was found to have an elevated NMR malignancy index comparable to that of malignant colon.

Breast

NMR in cancer. XI. Application of the NMR malignancy index to human gastro-intestinal tumors.

One hundred two specimens of human gastro-intestinal tissue taken from eighty-seven individuals were inspected by proton magnetic resonance techniques (at 22.5 Megahertz). The purpose of the study was to evaluate the diagnostic capabilities of the nuclear magnetic resonance (NMR) technique with regard to the diagnosis of malignancy. The combination of two NMR parameters (spin-lattice ((T1) and spin-spin ((T2)) relaxation times) into a malignancy index yielded complete discrimination between the two populations of tissue. The mean and standard deviations obtained were 2.004 +/- 0.342 for normal tissue, and 3.266 +/- 0.642 for malignant specimens. In addition, the NMR technique indicated that histologically normal tissue taken adjacent to the malignancy was pathologically "involved". Analysis of the electrolyte and water content of such tissues confirms this abnormality.

Digestive System

Whole-body nuclear magnetic resonance scanning: n.m.r. studies of tumour cells.

A technique, field-foxusing nuclear magnetic resonance (n.m.r.) spectroscopy (FONAR), is described for doing n.m.r. scans in large samples. The method utilizes a shaped d.c. magnetic field that confines the n.m.r. signal-producing region of the sample to a small volume called the resonance aperture. The aperture contains the required values of the Ho field to fully bracket the band of the r.f. pulse. The magnet system and r.f. pick-up coil that achieved the first human n.m.r. scan are discussed.

Abdominal Neoplasms

Field-focusing nuclear nuclear magnetic resonance (fomar).

A technique, field-focusing NMR (FONAR), is described for doing NMR scans in large samples. The method utilizes a shaped D.C. magnetic field that confines the NMR-signal-producing region of the sample to a small volume called the resonance aperture. The aperture contains the required values of the Ho field to fully bracket the band of the r.f. pulse. The magnet system and r.f. pick-up coil that achieved the first human NMR can is discussed.

Humans

NMR in cancer, XIII: application of the NMR malignancy index to human mammary tumours.

One hundred and nineteen specimens of human mammary tissue taken from 112 individuals, were inspected by pulsed proton magnetic-resonance techniques (at 22.5 MH2). The purpose of the study was to evaluate the diagnostic capabilities of the nuclear magnetic resonance (NMR) technique with regard to the recognition of malignancy. The combination of two NMR parameters (spin lattice (T1) and spin-spin(T2) relaxation times) into a malignancy index produced better than 95% discrimination between the 2 populations of tissue on a case-by-case basis. The mean and standard deviations obtained were 2.002 +/- 0.351 for normal tissue, and 3.137 +/- 0.667 for malignant specimens. The probability that this difference is not significant is considerably less than 0.01. In addition, specimens of fibrocystic disease and fibrous mastopathy had indices of 2.263 +/- 0.503 and 2.151 +/- 0.505 respectively. Both groups yielded P values less than 0.01 when compared to the malignant specimens.

Adenocarcinoma

Nuclear magnetic resonance in cancer, XII: Application of NMR malignancy index to human lung tumours.

Sixty specimens of human lung tissue from 52 individuals were inspected at 22.5 MHz by proton magnetic resonance techniques. The purpose of the study was to evaluate the diagnostic capabilities of the nuclear magnetic resonance (NMR) technique for the diagnosis of malignancy. The combination of two NMR parameters (spin-lattice (T1) and spin-spin (T2) relaxation times) into a malignancy index yielded 3 cases of overlap between the two populations of tissue. The mean and standard deviations obtained were 1.966 +/- 0.262 for normal tissue, and 2.925 +/- 0.864 for malignant specimens. In addition, analysis of the electrolyte and water content of the tissues confirm that factors other than specimen water content influence the relaxation time.

Humans

Biological ion exchanger resins: XI. Actin in Escherichia coli.

The 45,000 molecular weight component of an "actin-like" fraction (A-L fraction) from E. coli is identified as actin. Passage of skeletal muscle myosin through the A-L fraction specifically removes the 45,000 molecular weight band visible on electrophoresis prior to passage. Examination of the myosin after passage exhibits a new band on electrophoresis at 45,000 molecular weight.

Actins

Spectral differences in the 31P NMR of normal and malignant tissue.

High-resolution 31P NMR spectra of normal and malignant muscle tissue from mice were obtained at 100 MHz. The spectrum of normal muscle was found to resemble that obtained by Hoult et al. for normal rat skeletal muscle. But the spectrum of malignant muscle tumor (rhabdomyosarcoma) was found to comprise only the inorganic phosphate and sugar phosphate peaks, which indicates potential usefulness of this NMR method for diagnosis. Moreover, the inorganic phosphate peak was observed to be shifted downfield 70 Hz from the location seen in normal muscle. This identification of an NMR absorption frequency different in cancer tissue than in normal, singles out what may be the first of many absorption frequencies that could be utilized as target frequencies for delivery of cancer-destructive radiation.

Adenosine Diphosphate

Nuclear magnetic resonance chemical shifts of potassium ions (39K) on ion exchange resins and in muscle.

Chemical shifts of potassium (39K) were calculated from frequencies of beat patterns measured by a pulsed NMR method. This method indicates large chemical shifts for 3 molar KNO3 and 6 molal KI in good quantitative agreement with the steady state NMR measurements of previous investigators. 39K on two wet ion exchange resins and 39K in fresh muscle show insignificant chemical shifts relative to 0.1 M KCl solution. Previous studies showed marked shortening of NMR relaxation times (T1 and T2) for 39K in ion exchange resins and in muscle compared to free solution. These results seem to indicate that even though potassium on resins and in muscle experiences high electric field gradients, these have relatively little effect on the chemical shift of potassium, which may be correlated with the low pK values of the anionic groups in the resins and muscle.

Animals

NMR in cancer: VIII. Phosphorus-31 as a nuclear probe for malignant tumors.

Spin-lattice relaxation times (T1) for 31P were determined in normal and malignant tissues by a saturation technique employing a 90 degree -tau-90 degrees pulse sequence. Results for five normal tissues from rat were (in seconds): 2.33 +/- .14 for liver; 2.19 +/- .05 for muscle; 1.13 +/- .05 for brain; 1.43 +/- .15 fro kidney; and 1.97 +/- .12 for intestine. Results for two rat malignancies, Novikoff hepatoma and Walker sarcoma, were 5.98 +/- .57 and 5.38 +/- .68, respectively, and for Crocker sarcoma of mouse, 5.19 +/- 1.42. No individual measurement of malignant tissue overlapped any of the normal measurements; probabilities of insignificance ranged from .029 for Crocker sarcoma to .000184 for Novikoff hepatoma. The data call attention to another nucleus of potential value for NMR detection of internal malignancies in humans. Also suggested, because of the strategic placement of the 31P nucleus in the nucleic acid molecule, is a possible new probe for exploring the mechanism of carcinogenesis.

Animals