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H Poptani

Publications and source records attributed to H Poptani.

At least 19 recordsLinked to original sources
PubMed2005

In vivo and ex vivo MRI detection of localized and disseminated neural stem cell grafts in the mouse brain.

The application of stem cells as delivery vehicles opens up the opportunity for targeting therapeutic proteins to the damaged or degenerating central nervous system. Neural stem cell (NSC) lines have been shown to engraft, differentiate and correct certain central nervous system diseases. The present study was performed to test the ability of magnetic resonance imaging (MRI) in detecting transplanted NSCs under conditions of limited migration in the normal adult mouse brain versus widespread migration when the cells are transplanted neonatally. The C17.2 NSC line was labeled in vitro with superparamagnetic iron oxide (SPIO) particles and the labeled cells were implanted intracranially. Serial in vivo gradient echo MR imaging was performed using a 4.7 T horizontal bore magnet. High resolution ex vivo images of the isolated brains were performed at 9.4 T, and the presence of iron was correlated with Prussian blue staining in histological sections. Adult animals injected with SPIO-labeled stem cells exhibited hypointense regions near the injection site that were observed up to 32 days after injection. In neonatally transplanted animals, MR signal intensity from transplanted NSCs was not apparent in in vivo imaging but ex vivo MR images revealed small hypointense regions throughout the brain including the olfactory bulbs, cortex and the cerebellum, reflecting the wide distribution of the engrafted cells. These regions were correlated with Prussian blue staining, which confirmed the presence of SPIO particles inside the engrafted cells. We have shown that MRI is capable of differentiating localized and widespread engraftment of C17.2 stem cells in the central nervous system.

Animals↗
PubMed2002

Effects of hyperglycemia on oxygenation, radiosensitivity and bioenergetic status of subcutaneous RIF-1 tumors.

Since tissue oxygen tension is a balance between delivery and consumption of oxygen, considerable effort has been directed at increasing the former and/or decreasing the latter. Techniques to decrease the rate of cellular oxygen consumption (increasing the distance oxygen can diffuse into tissues) include increasing glycolysis by administering supra-physiologic levels of glucose. We have examined the effect of hyperglycemia produced by intravenous glucose infusion on the tissue oxygenation and radiation response of subcutaneously implanted murine radiation induced fibrosarcomas (RIF-1). A 0.3 M glucose solution was delivered via tail vein injection according to a protocol that maintained glucose at a plasma concentration of 17+/-1 mM. The effect of this treatment on radiation response (clonogenic and growth delay studies), tumor oxygenation (needle electrode pO2 and 2-[2-nitro-1H-imidazol-1-yl]-N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF5) binding), and tumor bioenergetics and pH (31P NMR spectroscopy) was examined. Systemic measurements included hematocrit and blood glucose and lactate concentrations. The results of these studies suggest that these subcutaneously implanted RIF-1 tumors are both radiobiologically and metabolically hypoxic and that intravenous glucose infusion is not an effective method of modifying this metabolic state.

Animals↗
PubMed2001

Quantitative T1rho magnetic resonance imaging of RIF-1 tumors in vivo: detection of early response to cyclophosphamide therapy.

This study compares two potential magnetic resonance imaging (MRI) indices for noninvasive early detection of tumor response to chemotherapy: the spin-lattice relaxation in the rotating frame (T1rho) and the transverse relaxation time (T2). Measurements of these relaxation parameters were performed on a s.c. murine radiation-induced fibrosarcoma (RIF-1) model before and after cyclophosphamide treatment. The number of pixels exhibiting T1rho values longer than controls in viable regions of the tumor increased significantly as early as 18 h after drug administration and remained elevated up to 36 h after treatment (P < 0.005). Although a trend of increasing T2s relative to controls was noted in viable regions of the tumor 36 h after treatment, the changes were not statistically significant. Histological examination indicated a decrease in mitotic index that paralleled the changes in T1rho. We conclude that T1rho measurements may be useful for noninvasive monitoring of early response of tumors to chemotherapy.

Animals↗
PubMed2001

Effects of chemotherapy by 1,3-bis(2-chloroethyl)-1-nitrosourea on single-quantum- and triple-quantum-filtered 23Na and 31P nuclear magnetic resonance of the subcutaneously implanted 9L glioma.

The effects of chemotherapy [25 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea administered with a single i.p. injection] on cellular energetics by 31P nuclear magnetic resonance (NMR) spectroscopy, total tissue sodium by single-quantum (SQ) 23Na NMR spectroscopy, and intracellular sodium by triple-quantum-filtered (TQF) 23Na NMR spectroscopy were studied in the s.c. 9L glioma. Animals were studied by NMR 2 days before therapy and 1 and 5 days after therapy. Destructive chemical analysis was also performed 5 days after therapy to validate the origin of changes in SQ and TQF 23Na signals. One day after treatment, there was no significant difference between control and treated tumors in terms of tumor size or 23Na and 31P spectral data. Five days after therapy, treated tumors had 28 +/- 16% (P < 0.1) lower SQ 23Na signal intensity, 46 +/- 20% (P < 0.05) lower TQF 23Na signal intensity, 125 +/- 51% (P < 0.05) higher ATP:Pi ratio, 186 +/- 69% (P < 0.05) higher phosphocreatine:Pi ratio, and 0.17 +/- 0.06 pH units (P < 0.05) higher intracellular pH compared with control tumors. No significant differences in TQF 23Na relaxation times were seen between control and treated tumors at any time point. Destructive chemical analysis showed that the relative extracellular space of control and treated tumors was identical, but the treated tumors had 21 +/- 8% (P < 0.05) lower total tissue Na+ concentration and 60 +/- 24% (P < 0.05) lower intracellular Na+ concentration compared with the controls. The higher phosphocreatine:Pi and ATP:Pi ratios after 1,3-bis(2-chloroethyl)-1-nitrosourea treatment indicate improved bioenergetic status in the surviving tumor cells. The decrease in SQ and multiple-quantum-filtered 23Na signal intensity was largely attributable to a decrease in Na(i)+ because the treatment did not change the relative extracellular space. The improved energy metabolism could decrease the intracellular concentration of Na+ by increasing the activity of Na+-K+-ATPase and decreasing the activity of Na+/H+. Although both 23Na and 31P spectra were consistent with improved cellular metabolism in treated tumors, the 23Na methods may be better suited for monitoring response to therapy because of higher signal:noise ratio and ease of imaging the single 23Na resonance.

Adenosine Triphosphate↗
PubMed2001

T1rho imaging of murine brain tumors at 4 T.

RATIONALE AND OBJECTIVES: The goal of this study was to evaluate the utility of T1rho weighting in magnetic resonance imaging of murine brain tumors. MATERIALS AND METHODS: S91 Cloudman melanoma was implanted in mouse brains (n = 4). A T2-weighted spin-echo (SE) and a T1rho-weighted fast SE-based sequence were performed on a 4-T clinical imager. T2 and T1rho maps were computed. The tumor-to-normal-tissue contrast was compared between T2-weighted, T1rho-weighted, proton-density-weighted, and pre- and postcontrast T1-weighted SE images. RESULTS: The tumor-tissue contrast of the T1rho-weighted images was similar to that of the T2-weighted images but less than that of the postcontrast T1-weighted images. The T1rho-weighted images provided better definition of tumor boundaries than T2-weighted images. At spin-locking powers of 0.5 and 1.5 kHz, the T1rho of the tumor was 64.0 msec +/- 0.46 and 68.65 msec +/- 0.59, respectively. There was no significant inter- or intra-animal variation in T1rho for tumor or normal brain cortex. CONCLUSION: T1rho-weighted imaging performed at low spin-lock strengths qualitatively depicted tumor borders better than proton-density or T2-weighted imaging and could be useful in treatment planning when combined with other imaging sequences.

Animals↗
PubMed2000

Lactate editing and lipid suppression by continuous wavelet transform analysis: application to simulated and (1)H MRS brain tumor time-domain data.

Determination of lactate concentrations in vivo is required in the noninvasive diagnosis, staging, and therapeutic monitoring of diseases such as cancer, heart disease, and stroke. An iterative filtering process based on the continuous wavelet transform (CWT) method in the time domain is proposed to isolate the lactate doublet signal from overlapping lipid resonances and estimate the magnetic resonance spectroscopy (MRS) parameters of the lactate methyl signal (signal amplitude, chemical shift, J-coupling and apparent transverse relaxation time (T*(2))). This method offers a number of advantages over the multiple quantum (MQ) and difference spectroscopy approaches, including: 1) full recovery of the lactate methyl signal, whereas the MQ methods usually detect 50% of the signal intensity; 2) in contrast to MQ methods, the lipid signal is retained together with J-coupling data on the lactate peak; 3) the CWT method is much less sensitive to motion artifacts than difference spectroscopy. Application of the method to simulated and real (1)H MRS data collected from human blood plasma and brain tumors demonstrated that this filter provides accurate estimates of the MRS parameters of the lactate doublet and efficiently removes lipid contributions.

Adult↗
PubMed1999

Diagnostic assessment of brain tumours and non-neoplastic brain disorders in vivo using proton nuclear magnetic resonance spectroscopy and artificial neural networks.

PURPOSE: Experiments were carried out to assess the potential of artificial neural network (ANN) analysis in the differential diagnosis of brain tumours (low- and high-grade gliomas) from non-neoplastic focal brain lesions (tuberculomas and abscesses), using proton magnetic resonance spectroscopy (1H MRS) as input data. METHODS: Single-voxel stimulated echo acquisition mode (STEAM) (echo time of 20 ms) spectra were acquired from 138 subjects including 15 with low-grade gliomas, 47 with high-grade gliomas, 18 with tuberculomas, 18 with abscesses and 40 healthy controls. Two neural networks were constructed using the spectral points from 0.6 to 3.4 parts per million. In the first network construction, the ANN had to differentiate between tumours from infections, while the second network had to differentiate between all five histological classes. RESULTS: ANN analysis gave a histologically correct diagnosis for low- and high-grade gliomas with an accuracy of 73% and 98% respectively. None of the 62 tumours was diagnosed as an infectious lesion. Among the non-neoplastic lesions, ANN classification was correct in 89% of tuberculomas and in 83% of brain abscesses. The specificity of ANN diagnosis was 98%, 92%, 99%, and 100% for low-grade gliomas, high-grade gliomas, tuberculomas and abscesses respectively. CONCLUSION: The present data show the clinical utility of non-invasive 1H MRS by automated ANN analysis in the diagnosis of tumour and non-tumour cerebral disorders.

Adolescent↗
PubMed1999

Low efficacy of gene therapy for rat BT4C malignant glioma using intra-tumoural transduction with thymidine kinase retrovirus packaging cell injections and ganciclovir treatment.

BACKGROUND: The purpose of this study was to test the use of Herpes Simplex virus thymidine kinase (HSVtk) retrovirus packaging cell injections in the treatment of malignant brain tumours. METHODS: Therapeutic effect and tissue responses were examined in vivo in a syngeneic BT4C rat glioma model after HSVtk-producing PA317 packaging cell injections and intraperitoneal ganciclovir (GCV) medication. MRI was used to visualise the tumours before and after the treatment. Immunohistochemical stainings were performed to study astroglia and microglia responses and apoptosis-mediated cell death. RESULTS: The results suggest that only a limited treatment effect can be achieved with HSVtk packaging cell injections with no prolonged survival rates. Histological examination showed a strong astroglia response but only a modest microglia response after the treatment. HSVtk and GCV-induced cell death was at least partially mediated by apoptosis. It is concluded that HSVtk packaging cell injections and GCV treatment do not lead to eradication of malignant cells in a syngeneic BT4C rat glioma model. The lack of efficacy is most likely due to low gene transfer efficiency and limited life span of the injected packaging cell inside the tumours. CONCLUSIONS: Improvements in gene transfer efficiency, and stimulation of immunoresponse against tumour cells might lead to a more effective therapeutic response in vivo.

Animals↗
PubMed1998

Quantitative 1H nuclear magnetic resonance diffusion spectroscopy of BT4C rat glioma during thymidine kinase-mediated gene therapy in vivo: identification of apoptotic response.

We have investigated the effects of thymidine kinase-mediated gene therapy in a malignant rat BT4C glioma by using 1H nuclear magnetic resonance spectroscopy in vivo. Ganciclovir has been successfully used in thymidine kinase gene therapy as treatment for various experimental malignancies. The cell damaging effect seems to be mediated by apoptosis, optimally leading to eradication of tumor tissue. In this study, we show that ganciclovir treatment of tumors transfected with the herpes simplex thymidine kinase gene causes profound changes in water, metabolites, and macromolecules observable by diffusion spectroscopy. During treatment, a 50% reduction from 0.14 +/- 0.01 x 10(-9) m2/s in the apparent diffusion coefficient of choline-containing compounds can be observed, concomitant with a 219% increase in the apparent diffusion coefficient of the rapidly diffusing water component. These changes are associated with an increase in the relative fraction of this water component from 87 to 94%. The apparent diffusion coefficients of the slowly diffusing water component and macromolecules remain unaltered. The results imply a reduction in cell size and number, a significant increase in intracellular viscosity, and a possible reduction in the hydrodynamic radii of macromolecular components, which are ascribed as biophysical signatures for apoptotic cell death.

Animals↗
PubMed1998

Role of in vivo proton magnetic resonance spectroscopy in the diagnosis and management of brain abscesses.

OBJECTIVE: In vivo proton magnetic resonance spectroscopy was performed for 24 patients with pyogenic brain abscesses, to examine the consistency of the spectral patterns and to observe the changes in metabolites with treatment. METHODS: Localized proton spectra were obtained from 4- to 8-ml volumes in the abscesses, using stimulated echo acquisition mode and spin echo sequences. Twenty-two patients were treated with combined surgical and medical therapy, and two patients were treated conservatively. High-resolution magnetic resonance spectroscopy was performed for 15 samples of abscesses obtained from these patients, to confirm the assignments of resonances seen in vivo. Postaspiration studies were performed for 12 patients treated with combined medical and surgical therapy and 2 patients treated medically. RESULTS: Lactate and amino acids were seen in spectra for all patients, irrespective of the time of spectroscopy after the onset of combined medical and surgical therapy. Acetate and pyruvate disappeared after 1 week of combined treatment. CONCLUSION: It was concluded that spectral patterns for brain abscesses are consistent and specific and can assist in the noninvasive diagnosis of abscesses. Responses to combined treatment could be monitored by showing the changes in metabolite patterns in serial spectroscopic studies.

Adolescent↗
PubMed1996

Finger printing of Mycobacterium tuberculosis in patients with intracranial tuberculomas by using in vivo, ex vivo, and in vitro magnetic resonance spectroscopy.

In vivo, ex vivo, and in vitro proton magnetic resonance spectroscopy was performed in 12 patients with intracranial tuberculomas with an aim of detecting the biochemical constituents of Mycobacterium tuberculosis in a granuloma. One dimensional (1D) single pulse and spin-echo sequences and 2D correlative spectroscopy were used for the ex vivo study to confirm the resonances seen on in vivo study. Spectroscopic studies of the perchloric acid and lipid extract of granuloma and M. tuberculosis were performed to look for similarity of resonance. In vivo study showed the presence of lipids at 0.9, 1.3, 2.0, 2.8 ppm, and phosphoserine at 3.7 ppm. All these resonances were confirmed on ex vivo study. In addition, distinct resonances of serine and phenolic lipids were seen on ex vivo and in vitro study of tuberculous granuloma, which have not been observed in other intracranial tumors. Lipid extract of granuloma and M. tuberculosis showed phenolic lipids at 7.1 and 7.4 ppm, a constituent of the cell wall of the bacteria in a tuberculoma. It appears that it may be possible to finger print the biochemicals of the cell wall of M. tuberculosis in a tuberculous granuloma and thus may help in detection and diagnosis of such lesions.

Amino Acids↗
PubMed1995

The magnetic resonance renogram in renal transplant evaluation using dynamic contrast-enhanced MR imaging.

To assess the role of the dynamic gadolinium DTPA (Gd-DTPA) magnetic resonance (MR) renogram in differentiating various causes of renal allograft dysfunction, contrast-enhanced MR imaging studies were performed in 5 normal renal allografts, 5 patients with acute rejection (AR), and 7 patients with cyclosporine nephrotoxicity. Time-versus-signal intensity (SI) curves were plotted. Normal renal allografts showed a rapid increase and slow decay, with a definite peak in cortical (CX) SI curves (peak mean signal intensity (Amax 338.6 +/- 46.5). The outer medullary (OM) (Amax 306.5 +/- 59) and inner medullary (IM) (Amax 263.4 +/- 47.4) curves did not show a definite peak. The OM curve slowly reached a steady state and caught up with the CX curve. AR episodes were characterized by a blunted uprise and delayed peak of CX (Amax 180 +/- 70.9) and a low-amplitude vascular phase with a slow constant uprise of the inner medullary curve (Amax 120.35 +/- 42.4). The OM signal intensity curve (Amax 150.73 +/- 78) failed to catch up with the CX curve. The maximum amplitude of SI curves in CsA-induced allograft dysfunction were low, with no definite peak, and CX, OM, and IM curves ran parallel to each other with a constant gap. Dynamic Gd-DTPA, MR imaging is a noninvasive technique that shows distinct characteristics in acute rejection, cyclosporine nephrotoxicity, and normally functioning renal allografts.

Adult↗
PubMed1995

Cystic intracranial mass lesions: possible role of in vivo MR spectroscopy in its differential diagnosis.

Thirty-four patients showing cystic intracranial mass lesions on MR imaging were evaluated by in vivo proton MR spectroscopy (MRS) with the aim of detecting lesion-specific spectral patterns that may assist imaging in better tissue characterization. In vivo spectroscopy was performed using stimulated echo acquisition mode with echo times 20 and 270 m in all, and spin echo with echo time 135 m in 11 patients. All primary neoplasms (intra-as well as extra-axial) showed choline (3.22 ppm) resonance along with lipid and/or lactate (1.3 ppm). It was not possible to grade cystic gliomas based on N-acetyl asparate-to-choline ratio. High-grade gliomas (n = 8) showed lipid/lactate and low-grade gliomas (n = 6) showed only lactate. Seven patients with brain abscess showed resonances only from acetate (1.92 ppm), lactate (1.3 ppm) and alanine (1.5 ppm). Two cases of metastatic adenocarcinoma showed only lipid/lactate. In 7 patients with epidermoid cyst, lactate along with an unassigned resonance at 1.8 ppm was observed and could be easily differentiated from arachnoid cysts (n = 2), which showed only minimal lactate. A case of cystic meningioma could be differentiated from cystic schwannoma by the presence of alanine in the former. It is concluded that MR imaging, when combined with in vivo MRS, may help to better characterize intracranial cystic mass lesions.

Brain↗
PubMed1995

Brain metabolite changes on in vivo proton magnetic resonance spectroscopy in children with congenital hypothyroidism.

Localized in vivo proton magnetic resonance spectroscopy and imaging were performed in five children with untreated congenital hypothyroidism to look for biochemical markers of abnormal myelin and neuronal development. The patients had high levels of choline-containing compounds, which returned to normal with euthyroidism. These metabolic alterations may reflect blocks in myelin maturation that are reversible by thyroid hormone replacement throughout childhood.

Adolescent↗
PubMed1995

In vivo proton magnetic resonance spectroscopy in a case of intracranial hydatid cyst.

We performed in vivo proton magnetic resonance spectroscopy (MRS) in a patient who had an intracranial hydatid cyst. Besides lactate, alanine, and acetate, a large resonance for pyruvate was observed. These findings were further confirmed by ex vivo high-resolution NMR spectroscopy of the evacuated cyst fluid, as well as of the fluid aspirated from a cyst in the liver of the same patient. The MRS pattern appeared different from that seen in other cystic lesions of the CNS. In vivo MRS may be used as an adjunct to imaging in the diagnosis of intracranial hydatid cysts. It may also have a role in monitoring drug therapy.

Brain Diseases↗
PubMed1995

Characterization of intracranial mass lesions with in vivo proton MR spectroscopy.

PURPOSE: To assess the use of in vivo proton MR spectroscopy for characterization of intracranial mass lesions and to ascertain its reliability in grading of gliomas. METHODS: One hundred twenty patients with intracranial masses were subjected to volume selective spectroscopy using stimulated echo acquisition mode (echo time, 20 and 270 milliseconds) and spin echo (echo time, 135 milliseconds) sequences. The intracranial lesions were grouped into intraaxial and extraaxial, as judged with MR imaging. Assignment of resonances was confirmed in two samples each of brain abscess, epidermoid cyst, and tuberculoma using ex vivo high-resolution MR spectroscopy. RESULTS: The in vivo spectra appeared distinct compared with normal brain in all the cases. All high-grade gliomas (n = 37) showed high choline and low or absent N-acetyl-L-aspartate and creatine along with lipid and/or lactate, whereas low-grade gliomas (n = 23) were characterized by low N-acetyl-aspartate and creatine and high choline and presence of only lactate. N-acetyl-aspartate/choline ratio was significantly lower and choline/creatine ratio was significantly higher in high-grade gliomas than in low-grade gliomas. Presence of lipids suggested a higher grade of malignancy. All metastases (n = 7) showed lipid and lactate, whereas choline was visible in only four cases. Epidermoids showed resonances from lactate and an unassigned resonance at 1.8 ppm. Meningiomas could be differentiated from schwannomas by the presence of alanine in the former. Among the infective masses, pyogenic abscesses (n = 6) showed resonances only from cytosolic amino acids, lactate, alanine, and acetate; and tuberculomas (n = 11) showed only lipid resonances. CONCLUSIONS: In vivo proton MR spectroscopy, helps in tissue characterization of intracranial mass lesions. Spectroscopy is a reliable technique for grading of gliomas when N-acetyl-aspartate/choline and choline/creatine ratios and presence of lipids are used in combination.

Adolescent↗
PubMed1995

In vivo localized proton magnetic resonance spectroscopy of intracranial tuberculomas.

In vivo proton magnetic resonance spectroscopy (MRS) was performed in ten patients with intracranial tuberculomas with the aim of finding biochemical finger prints which may help in the noninvasive diagnosis of the disease. Diagnosis of tuberculoma was confirmed in all these cases retrospectively. Ex vivo spectroscopy of formalin fixed samples of four granulomas and a normal brain (cerebellar) tissue, was performed to confirm the in vivo resonances. The in vivo study showed resonance at 1.3 ppm and 0.9 ppm assigned to methylene group (CH2)n and terminal methyl groups (-CH3) of fatty acids respectively which was subsequently confirmed by the ex vivo study. Large resonances of fatty acids in in vivo study appeared to be due to high lipid content of caseous material. It is concluded that in vivo proton spectroscopy may be helpful in differentiating tuberculomas from other intracranial mass lesions which have diagnostic difficulties on MR imaging.

Adult↗