Jongbin Lee

Measurement of brain tissue specific gravity using pycnometry

In this paper we introduce and characterize pycnometry, a method used to measure fluid density, for determining a tissues specific gravity. It uses a 2-ml glass pycnometer filled with distilled water to determine a tissue samples displacement volume. The tissues density is determined when its weight is divided by this volume and specific gravity is computed by dividing the tissue density by the density of water. Pycnometry was validated using pre-calibrated glass, specific gravity standards over the range 1.03-1.26, and compared to the density gradient method using rat brain tissue. We observed that the specific gravity values obtained using pycnometry were highly correlated with the specific gravity standards (slope = 1.0107, r = 0.996) and with the density gradient column when tissue volumes larger than 0.120 ml were used with the pycnometer (slope = 1.0707, r = 0.9826). Good correlation was also observed between percent water content values computed using the Nelson equation with pycnometry or density gradient specific gravity values versus the measured percent water content values obtained with the wet weight/dry weight method. Pycnometry is an accurate, reproducible technique to measure tissue specific gravity and brain edema and is best suited for use in a laboratory that engages sporadically in brain edema measurement.

“Artificial Lymphatic System”: A New Approach to Reduce Interstitial Hypertension and Increase Blood Flow, pH and pO2 in Solid Tumors

AbstractA mechanical drainage system, the “artificial lymphatic system” (ALS), consisting of a vacuum source and drain, is evaluated for its ability to aspirate the interstitial fluids responsible for the elevated interstitial fluid pressure (IFP) observed in solid tumors. IFP, pH, and pO2 radial profiles were measured before and after aspiration using wick-in-needle (WIN) probes, needle pH and oxygen electrodes, respectively. Laser Doppler flowmetry measured temporal changes in blood flow rate (BFR) at the tumor surface during aspiration. The WIN probe and IFP profile data were analyzed using numerical simulation and distributed mathematical models, respectively. The model parameter, pE reflecting central tumor IFP, was reduced from 15.3 to 5.7 mm Hg in neuroblastoma and from 13.3 to 12.1 mm Hg in Walker 256, respectively, following aspiration. The simulation demonstrated that spatial averaging inherent in WIN measurements reduced the calculated magnitude of the model parameter changes. IFP was significantly lower (p < 0.05), especially in regions surrounding the drain, and BFR was significantly higher (p < 0.05) following 25 and 45 min of aspiration, respectively; pH and pO2 profiles increased following aspiration. The experimental and mathematical findings suggest that ALS aspiration may be a viable way of reducing IFP and increasing BFR, pO2 and pH and should enhance solid tumor chemo and radiation therapy.

Changes in FDG Tumor Uptake during and after Fractionated Radiation Therapy in a Rodent Tumor Xenograft

OBJECTIVE: The uptake of FDG was measured before, during, and after fractionated radiation in order to evaluate the potential of FDG-PET imaging as an indicator of tumor response.METHODS: The study was performed with nude rats bearing the human neuroblastoma BE(2)C tumor xenografts. Tumors were irradiated with 10 fractions of 2 Gy using a 320 kV(p) X-ray unit. Following a baseline FDG-PET scan, repeat scans were performed weekly until animal sacrifice. The rodents were given up to 10 FDG-PET scans, over a period of up to 75 days posttreatment.RESULTS AND CONCLUSIONS: Neither, the average and maximum activity/cc of FDG tumor uptake, nor the respective standardized uptake values (SUV), correlated with tumor response. Instead, the total FDG uptake (defined as the product of the average FDG activity/cc with the tumor volume) correlated better with tumor response.

Enhancing the Uptake of Chemotherapeutic Drugs into Tumors using an “Artificial Lymphatic System”

AbstractThis paper presents findings from uptake studies to evaluate the ability of an “artificial lymphatic system” (ALS) to enhance large and small molecular weight drug transport into solid tumors and the therapeutic effect of the additional drug on their growth. These studies also served to test the effectiveness of an implantable multidrain ALS. Walker 256, Neuroblastoma, and Sarcoma dual-tumor models were used to evaluate the effect of ALS aspiration on the uptake of 3F8 monoclonal antibody, and doxorubicin. A tumor shrinkage experiment using Walker 256 dual tumors was used to evaluate the efficacy of an implantable ALS with cyclophosphamide chemotherapy. Drug uptake significantly increased in all aspirated tumors; 3F8 uptake was enhanced 37.4% in the Walker and 93.1% in the Neuroblastoma tumor lines (p < 0.05). Doxorubicin uptake increased 23.2%; in Sarcoma tumor (p < 0.05). The shrinkage study demonstrated that one-drain aspirated tumors shrank 90% faster (p < 0.01) than control tumors, while three-drain aspirated tumors shrank 123% faster than control tumors (p < 0.01).

The Effect of Lazaroid on Cerebral Elastance and Edema in a Cryogenic Injury Model

Lazaroid belongs to a novel group of compounds — aminosteroids (AS) which are potent inhibitors of central nervous system tissue lipid peroxidation, and are devoid of classical glucocorticoid and mineralocorticoid activities. Recent studies have shown that aminosteroids possess cerebral-protective properties and are efficacious in attenuating damage to the CNS imparted by trauma, ischemia, and vasospasm. The purpose of this study was to determine the effect of AS on (a) brain elastance, a measure of the protective volumetric buffering capacity of the brain, and (b) on cerebral perilesional edema. We used the cryogenic brain injury rat model, the constant rate and continuous infusion method to study brain elastance, and the gravitometric method to determine brain edema.