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Molecular imaging (MI) is a diverse technology that revolutionized preclinical, clinical and drug-discovery research. It integrates biology and medicine, and the technique presents a unique opportunity to examine living systems in vivo as a dynamic biological system. It is a hybrid technology that combines PET, SPECT, ultrasound, optical imaging and MR. Several MI methodologies are developed to examine the integrative functions of molecules, cells, organ systems and whole organisms. MI is superior to conventional diagnostic techniques in allowing better staging as well as to monitor the response of cancer/tumour to treatment. In addition, it helps visualization of specific molecular targets or pathways and cells in living systems and ultimately in the clinic. [ABSTRACT FROM AUTHOR]

Results of the proton magnetic resonance spectroscopy carried out on normal, benign breast disease and locally advanced breast cancer patients are presented. The in-vivo MR spectra of malignant breast tissue of patients (n = 67) suffering from infiltrating ductal carcinoma are dominated by the water resonance, while the spectra of the unaffected contralateral breast tissue of these patients are mainly dominated by resonance arising from lipids which is similar to the spectra of normal breast tissue obtained from volunteers (controls, n = 16). In addition to the water and lipid peaks, in majority of the patients (∼80%) the water suppressed spectra showed a resonance at 3.2 ppm due to choline containing compounds (TCho) before treatment. In patients receiving neoadjuvant chemotherapy, absence/reduction in choline was observed in 89% of the patients. TCho was also observed in 2 of 14 benign lesions. The sensitivity and specificity of in-vivo MRS in detecting TCho in malignant tumours was 78% and 86%, respectively. Observation of TCho before treatment and its disappearance (or reduction) after treatment may be a useful indicator of response of locally advanced breast cancer to neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) of skin has no standard treatment regimen, resulting in recurrences/metastasis. Although, doxorubicin (Dox), an anthracycline antibiotic has demonstrated some degree of efficacy. Molecular imaging can help in assessment of treatment response and prognosis of SCCs. MRI data showed that spin-spin relaxation (T2) time was longer (138 ± 2 msec) in Dox treated Test-II and there is no significant difference in spin-lattice relaxation (T1) time with respective controls. These findings further corroborated with the histology, proliferation index, apoptotic index, and HMGA1 protein expression. Thus, MRI may be a useful tool for monitoring treatment response noninvasively for skin tumor prognosis. [ABSTRACT FROM AUTHOR]

We evaluate the feasibility of proton magnetic resonance spectroscopy (1H MRS) using a spine coil receiver (body coil) in the diagnosis of carcinoma prostate. Seventeen patients with biopsy-proven prostate carcinoma, five patients of benign prostatic hyperplasia (BPH) and five healthy young volunteers underwent 1H MRS investigation. MRS was performed at 1.5 Tesla using a spine receiver coil for signal reception. In vivo citrate levels are reported as a ratio of citrate peak area to the sum of the areas of choline and creatine peak. MRS spectrum with good sensitivity and signal to noise (S/N) ratio was obtained in all 27 subjects. The citrate to creatine plus choline ratio was 0.31±0.25 in patients with cancer, 1.43±0.58 in BPH and 2.16±0.56 in controls. The difference in ratios between cancer and BPH and cancer and control was statistically significant (p<0.01). Within the cancer group, there was a statistically significant decline in levels with higher-grade malignancy (p<0.05). There were no complications of the procedure. There is a statistically significant decline in the ratio of citrate to choline plus creatine in the regions of cancer prostate when compared with BPH or normal control. The study demonstrates that MRS data can be reliably acquired using a spine coil receiver. MRS may also play a role in differentiating well-differentiated tumors from the anaplastic variety. [ABSTRACT FROM AUTHOR]

Cortical dynamics is driven by cortico-cortical connectivity and it characterizes cortical morphological features. These brain surface features complement volumetric changes and may offer improved understanding of disease pathophysiology. Hence, present study aims to investigate surface features; cortical thickness (CT) and gyrification index (GI) in Parkinson's disease (PD) patients of normal cognition (PD-CN), cognitively impaired patients with PD (PD-CI) in comparison with cognitively normal healthy controls (HC) to better elucidate cognition linked features in PD. Anatomical MRI (3DT1) was carried out in 30 HC (56.53 ± 8.42 years), 30 PD-CN (58.8 ± 6.07 years), and 30 PD-CI (60.3 ± 6.43 years) subjects. Whole brain ROI based parcellation using Desikan-Killiany (DK-40) atlas followed by regional CT and GI differentiation [with 'age' and 'total intracranial volume' (TIV) correction], multiple linear regression (with 'age', 'TIV', and 'education' correction) with clinical variables, ROC analysis, and CT-GI correlation across the groups was used for data analysis. Widespread cortical thinning with regional GI reduction was evident in PD-CI with respect to other two groups (HC and PD-CN), and with absence of such alterations in PD-CN compared to HC. Frontal, parietal, and temporal CT/GI significantly correlated with cognition and presented classification abilities for cognitive state in PD. Mean regional CT and GI were found negatively correlated across groups with heterogeneous regions. Fronto-parietal and temporal regions suffer cognition associated cortical thinning and GI reduction. CT may serve better discriminator properties and may be more consistent than GI in studying cognition in PD. Heterogeneous surface dynamics across the groups may signify neuro-developmental alterations in PD. [ABSTRACT FROM AUTHOR]

Magnetic resonance (MR) imaging is a useful tool to study the anatomy of the testis while 31P magnetic resonance spectroscopy (MRS) provides a non-invasive alternative method to demonstrate the metabolic status of testes. This study was designed to test whether the protective role of cyclosporine in experimental unilateral blunt testicular trauma (UBTT) could be assessed by 31P MRS. Male Wistar rats (n = 30) aged 20 days were randomised into group I (sham surgery), group II (UBTT) and group III (UBTT and cyclosporine for 7 days). Contralateral testicles of 5 rats from each group was evaluated by 31P MRS at 30 and 60 days of age and phosphomonoesters (PM), phosphodiesters (PD), and adenosine triphosphate (ATP) levels were measured. At 60 days of age the PM/ATP ratio was 0.32+/-0.08 in group I whereas it was 0.68+/-0.31 in the group II (p<0.05). Group III rats showed PM, PD and PM/ATP ratios similar to the controls. In conclusion, it is observed that UBTT causes contralateral testicular damage which could be prevented by short-term cyclosporine treatment and 31P MRS is an excellent modality for such an evaluation. [ABSTRACT FROM AUTHOR]

Background and purpose: Diagnosis of Parkinson's disease (PD) cognitive impairment at early stages is challenging compared to the stage of PD dementia where functional impairment is apparent and easily diagnosed. Hence, to evaluate potential early stage cognitive biomarkers, we assessed frontal lobe metabolic alterations using in vivo multi-voxel proton magnetic resonance spectroscopic imaging (1H-MRSI). Method: Frontal metabolism was studied in patients with PD with normal cognition (PD-CN) (n = 26), with cognitive impairment (PD-CI) (n = 27), and healthy controls (HC) (n = 30) using a single slice (two-dimensional) 1H-MRSI at 3 T. The acquired spectra were post-processed distinctly for voxels corresponding to the bilateral middle/superior frontal gray matter (GM) and frontal white matter (WM) regions (delineated employing neuromorphometrics atlas) using the LC-Model software. Result: Significant (post hoc p < 0.016) reduction in the concentration of N-acetyl aspartate (NAA) in the middle and superior frontal GMs and total choline (tCho) and total creatine (tCr) in the frontal WM was observed in PD-CI compared to PD-CN and HC, while that in HC and PD-CN groups were comparable. The NAA and tCr/tCho metabolite concentrations showed significant (p < 0.05) positive correlations with cognitive test scores in the frontal GM and WM, respectively. The receiver operating curve (ROC) analysis revealed significant (p < 0.05) "area under curve" for NAA/tNAA in the frontal GM and tCho in the frontal WM. Conclusion: The frontal metabolic profile is altered in cognitively impaired PD compared with cognitively normal PD. Neuronal function loss (NAA), altered energy metabolism (Cr), and cholinergic (Cho) neural transmission are implicated in PD cognitive pathology. Frontal neuro-metabolism may promisingly serve as PD cognitive biomarker. [ABSTRACT FROM AUTHOR]

Background The brain is a target for diabetic end-organ damage, though the pathophysiology of diabetic encephalopathy is still not well understood. The aim of the present study was to investigate the effect of diabetes on the metabolic profile of brain of patients having diabetes in comparison to healthy controls, using in-vivo magnetic resonance spectroscopy to get an insight into the pathophysiology of cerebral damages caused due to diabetes. Methods Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed at 1.5 T on right frontal, right parieto-temporal and right parieto-occipital white matter regions of the brain of 10 patients having type-2 diabetes along with 7 healthy controls. Absolute concentration of N-acetylaspartate (NAA), choline (cho), myo-inositol (mI), glutamate (Glu) and glutamine (Gln), creatine (Cr) and glucose were determined using the LC-Model and compared between the two groups. Results The concentration of N-acetylaspartate was significantly lower in the right frontal [4.35 ±0.69 vs. 5.23 ±0.74; p = 0.03] and right parieto-occipital region [5.44 ±0.52 vs.6.08 ±0.25; p = 0.02] of the brain of diabetics as compared to the control group. The concentrations of glutamate and glutamine were found to be significantly higher in the right frontal region of the brain [7.98 ±2.57 vs. 5.32 ±1.43; P = 0.01] in diabetics. Glucose levels were found significantly elevated in all the three regions of the brain in diabetics as compared to the control group. However, no significant changes in levels of choline, myo-inositol and creatine were observed in the three regions of the brain examined among the two groups. Conclusions 1H-MRS analysis indicates that type-2 diabetes mellitus may cause subtle changes in the metabolic profile of the brain. Decreased concentrations of NAA might be indicative of decreased neuronal viability in diabetics while elevated concentrations of Gln and Glu might be related to the fluid imbalance resulting from disruption of glucose homeostasis. [ABSTRACT FROM AUTHOR]

Mesenchymal epithelial transition factor (MET) is one of the critical cell signaling molecules whose aberrant expression is reported in several human cancers. The aim of the study is to investigate the antigene and antiproliferative effect of short triplex forming oligonucleotides, TFO-1 (part of the positive regulatory element) and TFO-2 (away from the transcription start site) on MET expression. HepG2 cells transfected only with TFO-1 (but not with TFO-2 and non-specific TFO) significantly decreased MET levels, which is accompanied by decrease in antiapoptotic proteins and increase in pro-apoptotic proteins. Phosphoproteome-array analysis of 46 intracellular kinases revealed hypophosphorylation of about 15 kinases including ERK, AKT, Src and MEK, suggesting the growth inhibitory effect of TFO-1. Further, the efficacy of TFO-1 was tested on diethylnitrosamine-induced liver tumors in wistar rats. T2-weighted magnetic resonance imaging showed decrease in liver tumor volume up to 90% after treatment with TFO-1. Decreased MET expression and elevated apoptotic activity further indicate that TFO-1 targeted to c-met leads to cell death and tumor regression in hepatoma. Formation of stable DNA triplex between TFO-1 and targeted gene sequence was confirmed by circular dichroic spectroscopy and gel retardation assay. Therefore, it can be concluded that DNA triplex-based therapeutic approaches hold promise in the treatment of malignancies associated with MET overexpression. [ABSTRACT FROM AUTHOR]

Context Vitamin D deficiency is prevalent worldwide. Vitamin D supplementation has shown variable effect on skeletal muscle strength in the elderly with hypovitaminosis D. There is a paucity of similar data in young individuals. Objective To study the effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in young individuals. Subjects Forty healthy volunteers (24M/16F, mean age (SD) 31·5 ± 5·0 year) with hypovitaminosis D were randomized to either oral cholecalciferol (60 000 IU D3/week for 8 weeks followed by 60 000 IU/month for 4 months) with 1 g of elemental calcium daily or dual placebos for 6 months. Measurements Handgrip and gastro-soleus dynamometry, pinch-grip strength, respiratory pressures, 6-min walk-test and muscle energy metabolism on 31P magnetic resonance spectroscopy were assessed at baseline and after 6 months. Results The mean serum 25(OH)D in the supplemented and placebo groups at baseline, two and 6 months were 25·4 ± 9·9, 94·5 ± 53·8 and 56·0 ± 17·0 nm, and 21·1 ± 9·4, 32·8 ± 14·4 and 29·7 ± 15·0 nm, respectively. The supplemented group gained a handgrip strength of 2·4 kg (95% C.I. = 1·2-3·6); gastro-soleus strength of 3·0 Nm (95% C.I. = 0·1-5·9) and walking distance of 15·9 m (95% C.I. = 6·3-25·5) over the placebo group after adjustment for age, gender and respective baseline parameters. Muscle energy parameters were comparable at 6 months. Conclusions Six months of cholecalciferol and calcium supplementation results in enhanced skeletal muscle strength and physical performance despite no change in muscle energy parameters. Cholecalciferol supplementation of 60 000 IU per month could not maintain 25(OH)D levels in the sufficient range. [ABSTRACT FROM AUTHOR]

Background & objectives: Repeated apnoeic/hypoapnoeic episodes during sleep may produce cerebral damage in patients with obstructive sleep apnoea (OSA). The aim of this study was to determine the absolute concentration of cerebral metabolites in apnoeic and non-apnoeic subjects from different regions of the brain to monitor the regional variation of cerebral metabolites. Methods: Absolute concentration of cerebral metabolites was determined by using early morning proton magnetic resonance spectroscopy (¹H MRS) in 18 apnoeic patients with OSA (apnoeics) having apnoea/ hypopnoea index (AHI) >5/h, while 32 were non-apnoeic subjects with AHI< 5/h. Results: The absolute concentration of tNAA [(N-acetylaspartate (NAA)+N-acetylaspartylglutamate (NAAG)] was observed to be statistically significantly lower (P<0.05) in apnoeics in the left temporal and left frontal gray regions compared to non-apnoeics. The GIx (glutamine, Gin + glutamate, Glu) resonance showed higher concentration (but not statistically significant) in the left temporal and left frontal regions of the brain in apnoeics compared to non-apnoeics. The absolute concentration of myo-inositol (ml) was significantly high (P<0.03) in apnoeics in the occipital region compared to non-apnoeics. Interpretation & conclusions: Reduction in the absolute concentration of tNAA in apnoeics is suggestive of neuronal damage, probably caused by repeated apnoeic episodes in these patients. NAA showed negative correlation with AH! in the left frontal region, while Cho and ml were positively correlated in the occipital region and GIx showed positive correlation in the left temporal region of the brain. Overall, our results demonstrate that the variation in metabolites concentrations is not uniform across various regions of the brain studied in patients with OSA. Further studies with a large cohort of patients to substantiate these observations are required. [ABSTRACT FROM AUTHOR]

Background: Cerebral vasospasm is a major cause of morbidity and mortality after subarachnoid hemorrhage (SAH). It usually occurs about 3-9 days after SAH. The pathogenesis involves the release of endogenous spasmogens. Though various treatment modalities are available, none are really effective. Aims and Objectives: The aim of the study was to develop an effective animal model for the study of SAH and vasospasm as well as to study the efficacy of vasodilators, namely nitroglycerine and papaverine, on SAH-induced vasospasm using magnetic resonance angiography. Materials and Methods: Fifteen Wistar albino rats, weighing around 150-200 gm were used for the study. Five rats served as controls of SAH-induced vasospasm, while five rats each were used to study the efficacy of intracisternal injection of papaverine or nitroglycerine. Results: Rats demonstrate vasospasm in a manner similar to humans. The maximal vasospasm is seen in the basilar artery. Statistical analysis demonstrates an improvement in vasospasm after instillation of intracisternal papaverine at the end of 2 hours in basilar and left internal cerebral artery. However, nitroglycerine does not produce any significant amelioration of vasospasm. Thus, it can be deduced that the pathogenesis of the vasospasm is more due to the action of cGMPase enzyme rather than inhibition of nitric oxide (NO) synthetase by the spasmogens. The present study is the first study in the English literature to compare the effects of single bolus doses of nitroglycerine and papaverine using magnetic resonance angiography. Conclusion: Rats can be used to create an effective model for SAH-induced vasospasm as the pattern resembles human SAH. Papaverine is an effective drug for ameliorating SAH-induced vasospasm. Short-acting NO donors are not as effective in ameliorating vasospasm. [ABSTRACT FROM AUTHOR]

The relationship between C-reactive protein (CRP), a marker of subclinical inflammation, and intramyocellular lipid (IMCL) content, a novel correlate of insulin resistance, has not previously been investigated. We estimated IMCL content in soleus muscle in 30 healthy Asian Indian males using proton magnetic resonance spectroscopy (1H MRS), and correlated it with body mass index (BMI), measures of abdominal obesity, percentage of body fat (%BF), serum lipoproteins, fasting and post-oral glucose load serum insulin levels and other surrogate markers of insulin resistance. Soleus muscle IMCL content was significantly correlated with age (ρ = 0·64, P < 0·001), BMI (ρ = 0·41, P < 0·05), %BF (ρ = 0·53, P ≤ 0·01), waist circumference (ρ = 0·45, P < 0·05) and waist-to-hip circumference ratio (ρ = 0·58, P < 0·01) but did not correlate significantly with insulin resistance measured by the homeostasis model assessment (HOMA-IR) or CRP levels. CRP levels did not correlate with the HOMA-IR value. Soleus muscle IMCL content correlated significantly with measures of generalized and abdominal obesity but not with insulin sensitivity or CRP levels in healthy Asian Indian males. Studies are needed in other ethnic groups to corroborate these data. [ABSTRACT FROM AUTHOR]

To evaluate brain metabolism and cerebral blood flow in young patients with hyperlipidaemia. Proton magnetic resonance spectroscopy (1H MRS) and single photon emission computed tomography (SPECT) of the brain was carried out in 19 asymptomatic young patients with hyperlipidaemia (mean age 32·6 ± 6·0 years, range 22–45 years) and 21 age-matched healthy controls divided into the following three groups; (i) hyperlipidaemics on pharmacological treatment (group 1, n = 13), (ii) hyperlipidaemics not on pharmacological treatment (group 2, n = 6) and (iii) control group of healthy subjects (group 3, n = 21). No statistical difference was observed in the brain metabolite ratios between controls and hyperlipidaemic patients (both treatment naive and treated) in the 1H NMR study. Two hyperlipidaemic patients showed a lactate peak and one had a lipid peak. The SPECT study was abnormal in seven hyperlipidaemic patients. In the pooled data, 50% subjects with high serum triglyceride (TG) levels as opposed to 14% subjects with normal serum TG levels showed cerebral hypoperfusion. The choline/creatine (Cho/Cr) ratio of the occipital region of the brain showed correlation with the excess percentage of body fat (%BF) and low levels of high density lipoprotein cholesterol (HDL-C) compared to those with normal %BF and normal HDL-C levels, respectively, in pooled data of all subjects. The N-acetyl aspartate (NAA)/Cho ratio also showed correlation with hypercholesterolaemia. Serum TG levels were positively correlated with the NAA/Cr ratio ( r = 0·62, P < 0·05) and the Cho/Cr ratio ( r = 0·63, P < 0·05) in the parieto-temporal area in group 1 patients. The study revealed no difference in the brain metabolite ratios between controls and hyperlipidaemic patients, while some hyperlipidaemic patients showed abnormalities of cerebral blood flow. Brain metabolite ratios were also influenced by certain parameters of body composition and lipids. As abnormal body composition, hypertriglyceridaemia and low levels of HDL-C are prevalent in Asian Indians, such data are important and indicate a need for further study. [ABSTRACT FROM AUTHOR]

Neuropsychiatric involvement in SLE (NP-SLE) may not be picked up by routine neuroimaging procedures like computerized tomography (CT) or magnetic resonance imaging (MRI). We prospectively studied the role of single photon emission computerized tomography (SPECT) and magnetic resonance spectroscopy (MRS) in detection of NP-SLE in 20 patients with lupus (10 with clinical NP involvement and 10 without) and 9 healthy controls. MRI abnormalities were seen in 5/10 patients with NP-SLE while the MRI was normal in all the lupus patients without clinical NP involvement. Perfusion defects on SPECT were seen in as many as 8/10 patients with NP-SLE while only 1/10 lupus patients without clinical NP involvement and none of the healthy controls demonstrated perfusion defects. MRS revealed abnormal metabolite ratios in all patients with NP-SLE and as many as 8 lupus patients without clinical NP features. Normal metabolite ratios were observed in healthy controls. SPECT and MRS can help detect changes not evident on MRI and may serve as useful supplements to existing neuroimaging techniques in the diagnosis of NP-SLE. The precise significance of alterations in regional cerebral blood flow on SPECT and neurometabolite ratios on MRS needs larger, longitudinal studies. [Copyright &y& Elsevier]

Abstract Aims Intramyocellular lipids (IMCL) appears to be important in the pathogenesis of insulin resistance. Correlation of IMCL content of soleus muscle with insulin sensitivity has been reported in the Caucasian population. In the present study, IMCL content was estimated in the soleus muscle of both non-obese healthy males and Type 2 diabetic males, and correlated with the anthropometric parameters, blood glucose, plasma lipids, and insulin resistance in Asian Indians from North India. Methods Twenty males (Type 2 diabetes mellitus 10; healthy controls 10) with body mass index (BMI) ≤ 25 kg/m2 were recruited in the study. In both healthy and diabetic groups, five subjects had percentage body fat (%BF) ≤ 25, and other five subjects had percentage BF > 25. The following were assessed in all subjects: body composition, fasting blood glucose, lipid profile, insulin levels, insulin resistance by homeostasis model assessment, and proton magnetic resonance spectroscopy (1 H MRS) study of the soleus muscle. Results IMCL content was approximately two times higher in Type 2 diabetic males compared with healthy males (P < 0.05). Amongst healthy males, IMCL content was significantly higher (P < 0.05) in subjects with percentage BF > 25 compared with subjects with percentage BF ≤ 25. Similarly, IMCL content was high in subjects with waist–hip ratio (WHR) > 0.95 compared with subjects with WHR ≤ 0.95. In healthy males but not in diabetic males, positive significant correlation of IMCL content of soleus muscle was observed with waist circumference (r = 0.73, P < 0.05) and WHR (r = 0.71, P < 0.05). However, IMCL content did not correlate significantly to insulin resistance in both the groups. Conclusions 1 H MRS study of soleus muscle in a small sample of non-obese Asian Indians showed higher IMCL content in Type 2 diabetics compared with healthy subjects. Non-obese healthy male subjects having high percentage BF and WHR also had high IMCL content, and it significantly correlated to waist circumference and WHR. However, lack of relationship of IMCL content with insulin resistance in Asian Indians needs further study. Diabet. Med. 20, 361–367 (2003). [ABSTRACT FROM AUTHOR]

Bilaterally absent vas deferens is a surgically uncorrectable cause of male infertility. It is usually diagnosed clinically. We evaluate the role of semen analysis and radiological imaging in providing objective evidence of vas aplasia. Twenty consecutive patients with clinically suspected bilateral vas aplasia were enrolled for this prospective study. They were investigated on the basis of an algorithm till corroborative evidence for vas aplasia was obtained. This successively included a semen analysis on at least two occasions, transrectal ultrasonogram (TRUS), pelvic magnetic resonance imaging (MRI) and scrotal exploration. The contribution of each investigation to confirming the diagnosis was evaluated. Seventeen patients (85%) had a low volume ejaculate while all 20 had azoospermia and semen fructose levels below normal. Semen pH was non-acidic in 75% of cases and thus was not contributory to the diagnosis. TRUS and MRI were non-contributory in 30% and 50% of evaluations, respectively. The clinical diagnosis was found to be correct in all patients. Vas aplasia is a clinical diagnosis. Low volume ejaculate with azoospermia and low or absent semen fructose is sufficient corroborative evidence and no further investigations are required for this diagnosis. [ABSTRACT FROM AUTHOR]