Bio-energetic impairment in human calf muscle in thyroid disorders: a P MRS study

Mitochondrial metabolism particularly oxidative phosphorylation is greatly influenced by thyroid hormones. Earlier studies have described neuromuscular symptoms as well as impaired muscle metabolism in hypothyroid and hyperthyroid patients. In this study, we intend to look in to the muscle bioenergetics including phosphocreatine recovery kinetics based oxidative metabolism in thyroid dysfunction using in vivo ³¹P nuclear magnetic resonance spectroscopy (MRS). ³¹P MRS was carried out at resting state on 32 hypothyroid, 10 hyperthyroid patients and 25 control subjects. Nine out of 32 hypothyroid patients and 17 out of 25 control subjects under went exercise protocol for oxidative metabolism study and performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr), phosphodiesters (PDE) and adenosine triphosphate (ATP) of the calf muscle were acquired during rest, exercise and recovery phase. PCr recovery rate constant (k_PCr) and oxidative capacity were calculated by monoexponential fit of PCr versus time (t) at the beginning of recovery. During resting condition in hypothyroid patients, PCr/Pi ratio was reduced whereas PDE/ATP and Pi/ATP were increased. However, in case of hyperthyroidism, an increased PCr/Pi ratio and reduced PDE/ATP and Pi/ATP were observed. The results confirmed differential energy status of the muscle due to increased or decreased levels of thyroid hormone. Our results also demonstrate reduced oxidative metabolism in hypothyroid patients based on PCr recovery kinetics. PCr recovery kinetics study after exercise revealed decreased PCr recovery rate constant (k_PCr) in hypothyroid patients compared to controls that resulted in decrease in oxidative capacity of muscle by 50% in hypothyroids. These findings are consistent with a defect of high energy phosphate mitochondrial metabolism in thyroid dysfunction.     

High-energy phosphate metabolism during incremental calf exercise in humans measured by 31 phosphorus magnetic resonance spectroscopy (31P MRS)

Several previous 31 phosphorus magnetic resonance spectroscopy ((31)P MRS) studies performing incremental or progressive muscle exercises have observed that a decrease in pH is accompanied with an acceleration in phosphocreatine (PCr) hydrolysis. The purpose of this study was to investigate the relationship between PCr breakdown and pH during isotonic, exhaustive, incremental plantar flexion exercises. We included eight healthy, male volunteers into this study. Using a 1.5 Tesla MR scanner and a self-built exercise bench, we performed serial free induction decay (FID) (31)P MRS measurements with a time resolution of 1 min at rest, isotonic calf muscle exercise, and recovery. The exercise protocol consisted of 5-min intervals with 4.5, 6, 7.5, and 9 W workload followed by 9-min recovery. Changes in PCr and inorganic phosphate (Pi) were determined as percent changes in comparison to the baseline. In addition, pH values were calculated. This study obtained significant decreases in PCr corresponding to the gradual increases in workload. In each workload level that was succeeded by all volunteers, PCr hydrolysis passed into a steady state. After an early biphasic response, we detected a significant decrease in pH from the first to the second minute of the 6-W workload level followed by a further continuous decrease in pH up to the second minute of the recovery phase. The decrease in pH was not accompanied by acceleration in PCr hydrolysis. In conclusion, this study shows that PCr hydrolysis during incremental plantar flexion exercises passes into a steady state at different workload levels. The observed decrease in pH does not result in acceleration of PCr hydrolysis.     

In vivo (31)P MRS study of skeletal muscle metabolism in patients with postpolio residual paralysis

The muscle metabolism of at-rest patients with varying degrees of postpolio residual paralysis (PPRP) was studied and compared with that of controls using in vivo phosphorus magnetic resonance spectroscopy. The phosphocreatine (PCr)/inorganic phosphate (Pi) and PCr/adenosine triphosphate ratios were lower in patients than in controls. Reduction in PCr/Pi suggests abnormalities in oxidative phosphorylation. A significant increase was observed in the phosphomonoester/PCr ratio in patients, indicating the accumulation of intermediary compounds of the glycolytic pathway. Furthermore, the phosphodiester/PCr ratio was also significantly increased in patients. In general, the observed changes in metabolite ratios were found to be related to the degree of residual paralysis, suggesting that metabolic changes are secondary to chronic neurogenic processes. These metabolic alterations appear to be the possible cause of energy deficit and underlying muscle fatigue in PPRP patients. The present results provide an insight into the metabolic impairment and degree of muscle damage in patients with PPRP.     

In vivo 31P-MRS assessment of muscle-pH, cytolsolic-[Mg2+] and phosphorylation potential after supplementing hypokaliuric renal stone patients with potassium and magnesium salts

Renal stone patients in rural northeast Thailand have a low potassium and magnesium status and low urinary excretion of citrate. We measured the changes of urinary citrate excretion and assessed in vivo skeletal muscle metabolism for intracellular-pH, cytosolic-[Mg(2+)] and phosphorylation potential (using the phosphorus magnetic resonance spectroscopy (31)P-MRS) after oral supplementation to hypokaliuric renal stone patients with oral potassium and magnesium salts. The patients comprised four groups: Group 1 (n = 10) control, Group 2 (n = 3), Group 3 (n = 5) and Group 4 (n = 6) supplemented for a month with potassium citrate, potassium citrate plus amino acid chelated magnesium, and potassium-magnesium citrate, respectively. Though urinary citrate excretion was increased in all three supplemented groups, the increases in intracellular-pH, cytosolic-[Mg(2+)] and phosphocreatine (PCr)/beta-ATP were prominent only in Group 3. The increase in PCr/beta-ATP was also observed in Group 4.     

Quantitative Evaluation of Oxygenation and Metabolism in the Human Skeletal Muscle

The forearm muscles of five healthy males were monitored for changes in microvessel hemoglobin saturation (SO_2-TRS) by near infrared time-resolved spectroscopy (NIR_TRS) and changes in phosphorus metabolites by magnetic resonance spectroscopy (³¹P-MRS) during 12 min of resting arterial occlusion. Muscle oxygenation and phosphorus metabolites were also measured during grip exercises at varying intensities. Upon the initiation of occlusion, SO_2-TRS fell progressively until it reached a plateau in the latter half of the occlusion. Phosphocreatine (PCr) began to decrease around 6 min after the initiation of arterial occlusion. The resting O₂ store and O₂ consumption were 295 μM and 0.95 μM/sec, respectively-values which reasonably agree with the reported results. A significant correlation was observed between the changes in SO_2-TRS and PCr during exercise (r² = 0.80, p < 0.001). These results indicate that NIR_TRS is able to provide reliable information about resting metabolism and oxidative rate during exercise. NIR_TRS and MRS are useful to monitor oxygenation and energetics noninvasively in the human muscle.     

Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized,placebo-controlled P MRS study

Randomized, placebo-controlled single blinded study was carried out to evaluate the effect of oral creatine supplementation on cellular energetics, manual muscle test (MMT) score and functional status in steroid-naive, ambulatory boys suffering with Duchenne muscular dystrophy (DMD; n=33). Eighteen patients received creatine monohydrate (Cr; 5 g/day for 8 weeks), while 15 received placebo (500 mg of vitamin C). Phosphorus metabolite ratios were determined from the right calf muscle of patients using phosphorus magnetic resonance spectroscopy (³¹P MRS) both prior to (baseline) and after supplementation of Cr or placebo. In addition, metabolite ratios were determined in normal calf muscle of age and sex matched controls (n=8). Significant differences in several metabolite ratios were observed between controls and DMD patients indicating a lower energy state in these patients. Analysis using analysis of covariance adjusted for age and stature showed that the mean phosphocreatine (PCr)/inorganic phosphate (Pi) ratio in patients treated with Cr (4.7; 95% CI; 3.9–5.6) was significantly higher (P=.03) compared to the placebo group (3.3; 95% CI; 2.5–4.2). The mean percentage increase in PCr/Pi ratio was also more in patients <7 years of age compared to older patients after Cr supplementation indicating variation in therapeutic effect with the age. In the placebo group, significant reduction in PCr/Pi (P=.0009), PCr/t-ATP (P=.05) and an increase in phosphodiester (PDE)/PCr ratios was observed after supplementation. Further, in the placebo group, patients <7 years showed reduction of PCr/t-ATP and Pi/t-ATP compared to older patients (>7 years), after supplementation. These results imply that the significant difference observed in PCr/Pi ratio between the Cr and the placebo groups after supplementation may be attributed to a decrease of PCr in the placebo group and an increase in PCr in the Cr group. Changes in MMT score between the two groups was significant (P=.04); however, no change in functional scale (P=.19) was observed. Parents reported subjective improvement on Cr supplementation versus worsening in placebo (P=.02). Our results indicated that Cr was well tolerated and oral Cr significantly improved the muscle PCr/Pi ratio and preserved the muscle strength in short term. However, this study provides no evidence that creatine will prove beneficial after long-term treatment, or have any positive effect on patient lifespan.     

急性低氧大鼠脑31P核磁共振波谱研究

³¹P磁共振波谱是目前唯一可以用作在体无损伤的检测细胞水平能量代谢变化的非侵入性技术,可测得脑内多种能量代谢产物.目的：急性低氧大鼠脑组织的³¹P MRS检测.方法：(1)20只成年SD大鼠分为4组：低氧0min(对照),5min,10min,15min后,迅速液氮冷冻;(2)将脑组织研碎后,加入高氯酸(PCA),冷冻干燥;(3)将提取物用0.5mL D\-2O溶解后进行MRS检测.结果：(1)急性低氧早期即引起³¹P MRS中PCr和ATP峰降低,ADP和Pi峰增高,PCr/Pi和ATP/Pi降低,而ADP/ATP增高.可交换磷池(EPP)中PCr的正常值为42.4%,低氧5min后降到28.9%, ATP从33.8%降到19.2%,Pi从17.7%升到42.0%.(2)急性低氧时³¹P MRS中脑内磷酯分解代谢产物GPC、GPE含量增加,说明低氧早期脑内即有膜磷酯的分解增加.结论：³¹P磁共振波谱可用于脑低氧性疾病的诊断,我们波谱中最敏感的指标是PCr/Pi和ATP/Pi,尤其早期降低更为显著.     

31P-spectroscopy of head and neck tumors--surface coil technique

Comparative phosphorus-31 magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) of 15 patients with superficial masses such as sarcoma, carcinoma, lymphoma, adenoma, and tuberculosis revealed significant increased concentrations of phosphomonoester, phosphodiester, and inorganic phosphorus in the lesion, whereas the concentration of the phosphocreatine was lower in comparison to muscle tissue. In nearly all masses, pH showed a slight alkaline shift. Existence of necrotic regions detected by MRI was marked by an increase of inorganic phosphorous in the spectra. Tumor growth was characterized by raised concentrations of phosphomonoester. Follow-up studies in a case of lymphoma showed a six-fold decrease of the tumor, while the spectra indicated a gradual transition of tumor values to muscle values. A follow-up study during irradiation of a squamous cell carcinoma revealed a considerable decrease of inorganic phosphate and a subsequent increase of phosphodiester.     

Time averaging and fitting of nonlinear metabolic changes: the issue of the time index choice applied to 31P MRS investigation of muscle energetics

We present an exact analytical method dedicated to fitting time-dependent exponential-like changes in MR spectra. As an illustration, this method has been applied to fitting metabolic changes recorded by 31P MRS in human skeletal muscle occurring during a rest-exercise-recovery protocol. When recording metabolic changes with the accumulative method, the time averaging of the MR signals implies the choice of a time index for fitting any changes in the features of the associated MR spectra. A critical examination of the different ways (constant, linear, and exponential) of choosing the time index is reported. By numerical analysis, we have calculated the errors generated by the three methods and we have compared their sensitivity to noise. In the case of skeletal muscle, both constant and linear methods introduce large and uncontrolled errors for the whole set of metabolic parameters derived from [PCr] changes. In contrast, the exponential method affords a reliable estimation of critical parameters in muscle bioenergetics in both normal and pathological situations. This method is very easy to implement and provides an exact analytical solution to fitting changes in MR spectra recorded by the accumulative method.     

The effect of orientation on quantification of muscle creatine by 1H MR spectroscopy

Creatine is a central energy metabolite whose N-CH3 group can be detected with 1H MR spectroscopy (1H MRS) with relatively high sensitivity. Prior studies suggest that muscle fiber orientation can influence the appearance of other resonances attributed to total creatine (CR). Our purpose was to determine whether muscle fiber orientation affects muscle CR concentration quantification by 1H MRS with the commonly used N-CH3 resonance at 3.0 ppm. Skeletal muscle CR was quantified with water-referenced 1H MRS in normal subjects with different forearm muscle orientations relative to the static magnetic field at 1.5T. There were no significant differences in mean total [CR] in two different series of experiments separately including two orthogonal orientations and four orientations (0 degrees, 30 degrees, 60 degrees, 90 degrees) of the forearm relative to the static field using either short (TE = 15 ms) or long (TE = 100 ms) echo times for voxels containing or centered on the same tissues. Subtle differences in CR line-width and T2 correction factors were observed with orientation. These observations are consistent with the primary hypothesis that careful water-referenced [CR] quantification, accounting for T2 effects and using the N-CH3 peak at 3.0ppm, is not affected by muscle orientation.     

In vivo 31P MRS of human brain at high/ultrahigh fields: a quantitative comparison of NMR detection sensitivity and spectral resolution between 4 T and 7 T

The primary goal of this study was to establish a rigorous approach for determining and comparing the NMR detection sensitivity of in vivo ³¹P MRS at different field strengths (B₀). This was done by calculating the signal-to-noise ratio (SNR) achieved within a unit sampling time at a given field strength. In vivo ³¹P spectra of human occipital lobe were acquired at 4 and 7 T under similar experimental conditions. They were used to measure the improvement of the human brain ³¹P MRS when the field strength increases from 4 to 7 T. The relaxation times and line widths of the phosphocreatine (PCr) resonance peak and the RF coil quality factors (Q) were also measured at these two field strengths. Their relative contributions to SNR at a given field strength were analyzed and discussed. The results show that in vivo ³¹P sensitivity was significantly improved at 7 T as compared with 4 T. Moreover, the line-width of the PCr resonance peak showed less than a linear increase with increased B₀, which leads to a significant improvement in ³¹P spectral resolution. These findings indicate the advantage of high-field strength to improve in vivo ³¹P MRS quality in both sensitivity and spectral resolution. This advantage should improve the reliability and applicability of in vivo ³¹P MRS in studying high-energy phosphate metabolism, phospholipid metabolism and cerebral biogenetics in the human at both normal and diseased states noninvasively. Finally, the approach used in this study for calculating in vivo ³¹P MRS sensitivity provides a general tool in estimating the relative NMR detection sensitivity for any nuclear spin at a given field strength.     

Serial Precision of Metabolite Peak Area Ratios and Water Referenced Metabolite Peak Areas in Proton MR Spectroscopy of the Human Brain

The precision of cerebral proton magnetic resonance spectroscopy (MRS) measurements is critical both in the clinical setting and for research purposes. Marshall et al. have recently concluded that “disappointing in vivo repeatability…is likely to limit” the ability of MRS to detect modest changes. We present here a comprehensive study of the precision of short- and long-term metabolite peak area ratios and water referenced metabolite peak areas for long echo time point resolved spectroscopy (PRESS) spectra (repetition time (TR) = 2000 ms, echo time (TE) = 136 ms) acquired from the occipital lobes of normal volunteers and a phantom using a conventional whole body 1.5 T MR system and conventional acquisition and analysis protocols. Short-term in vitro precision determined by five repeat scans on five occasions was excellent as measured by a mean coefficient of variation (NAA/Cho = 1.3%, NAA/Cr + PCr = 1.0%, Cho/Cr + PCr = 1.6%, NAA/H₂O = 0.5%, Cho/H₂O = 1.2%, Cr + PCr/H₂O = 0.8%). Long term in vitro precision using 100 spectra acquired over 2 years was also very good (NAA/Cho = 2.7%, NAA/Cr + PCr = 1.4%, Cho/Cr + PCr = 2.2%, NAA/H₂O = 1.5%, Cho/H₂O = 2.4%, Cr + PCr/H₂O = 1.5%). Short-term in vivo precision determined by five repeat scans in a single scanning session on eight subjects was also excellent (NAA/Cho = 5.2%, NAA/Cr + PCr = 3.0%, Cho/Cr + PCr = 6.6%, NAA/H₂O = 1.4%, Cho/H₂O = 4.9%, Cr + PCr/H₂O = 2.7%) and only worsened slightly for long-term in vivo precision determined by five repeat scans on eight subjects over 3 months (NAA/Cho = 5.2%, NAA/Cr + PCr = 4.8%, Cho/Cr + PCr = 7.7%, NAA/H₂O = 2.5%, Cho/H₂O = 6.4%, Cr + PCr/H₂O = 3.8%). We attribute the excellent precision reported here to the use of highly automated techniques for voxel shimming, water suppression and peak area measurements. These results allow us to repudiate Marshall’s assertion regarding disappointing repeatability of in vivo MRS.     

The feasibility of assessing branched-chain amino acid metabolism in cellular models of prostate cancer with hyperpolarized [1-C]-ketoisocaproate

Recent advancements in the field of hyperpolarized ¹³C magnetic resonance spectroscopy (MRS) have yielded powerful techniques capable of real-time analysis of metabolic pathways. These non-invasive methods have increasingly shown application in impacting disease diagnosis and have further been employed in mechanistic studies of disease onset and progression. Our goals were to investigate branched-chain aminotransferase (BCAT) activity in prostate cancer with a novel molecular probe, hyperpolarized [1-¹³C]-2-ketoisocaproate ([1-¹³C]-KIC), and explore the potential of branched-chain amino acid (BCAA) metabolism to serve as a biomarker. Using traditional spectrophotometric assays, BCAT enzymatic activities were determined in vitro for various sources of prostate cancer (human, transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse and human cell lines). These preliminary studies indicated that low levels of BCAT activity were present in all models of prostate cancer but enzymatic levels are altered significantly in prostate cancer relative to healthy tissue. The MR spectroscopic studies were conducted with two cellular models (PC-3 and DU-145) that exhibited levels of BCAA metabolism comparable to the human disease state. Hyperpolarized [1-¹³C]-KIC was administered to prostate cancer cell lines, and the conversion of [1-¹³C]-KIC to the metabolic product, [1-¹³C]-leucine ([1-¹³C]-Leu), could be monitored via hyperpolarized ¹³C MRS.     

In vivo C magnetic resonance spectroscopy of a human brain tumor after application of C-1-enriched glucose

Objectives

As a unique tool to assess metabolic fluxes noninvasively, ¹³C magnetic resonance spectroscopy (MRS) could help to characterize and understand malignancy in human tumors. However, its low sensitivity has hampered applications in patients. The aim of this study was to demonstrate that with sensitivity-optimized localized ¹³C MRS and intravenous infusion of [1-¹³C]glucose under euglycemia, it is possible to assess the dynamic conversion of glucose into its metabolic products in vivo in human glioma tissue.

Materials and Methods

Measurements were done at 3 T with a broadband single RF channel and a quadrature ¹³C surface coil inserted in a ¹H volume coil. A ¹H/¹³C polarization transfer sequence was applied, modified for localized acquisition, alternatively in two (50 ml) voxels, one encompassing the tumor and the other normal brain tissue.

Results

After about 20 min of [1-¹³C]glucose infusion, a [3-¹³C]lactate signal appeared among several resonances of metabolic products of glucose in MR spectra of the tumor voxel. The resonance of [3-¹³C]lactate was absent in MR spectra from contralateral tissue. In addition, the intensity of [1-¹³C]glucose signals in the tumor area was about 50% higher than that in normal tissue, likely reflecting more glucose in extracellular space due to a defective blood–brain barrier. The signal intensity for metabolites produced in or via the tricarboxylic acid (TCA) cycle was lower in the tumor than in the contralateral area, albeit that the ratios of isotopomer signals were comparable.

Conclusion

With an improved ¹³C MRS approach, the uptake of glucose and its conversion into metabolites such as lactate can be monitored noninvasively in vivo in human brain tumors. This opens the way to assessing metabolic activity in human tumor tissue.     

Tin-mono-sulfide (SnS) thin films prepared by chemical spray pyrolysis with different [S]/[Sn] ratios

SnS thin films were deposited by chemical spray pyrolysis using cost-effective and low-toxicity sources materials like tin (II) chloride dihydrate and thiourea as sources of tin and sulphur, respectively. We have studied the properties of sprayed SnS thin films with [S]/[Sn] ratios were varied from 1 to 4 in order to optimize these parameters. X-ray diffraction was used for analyzing the films structure, Raman Spectroscopy for assessing the films quality and structure, scanning electron microscope (SEM) for surface morphology and energy dispersive energy (EDS) for compositional element in samples, atomic force microscopy (AFM) for the topography of surfaces and optical spectroscopy for measuring transmittances and then deducing the band gap energies. All films obtained are polycrystalline with (111) as preferential direction for films with [S]/[Sn] ratio equals to one while for [S]/[Sn] ratios from 2 to 4 the main peak becomes (101) and the (111) peak decreases in intensity. Raman spectroscopy confirms the presence of only one SnS phase without any additional parasite secondary phases. SEM images revealed that films are well adhered onto glass surface with rounded grain. AFM confirms this result being films with [S]/[Sn] = 1 the roughest and also with the largest grain size. EDS results show an improvement of stoichiometry with the increase of the [S]/[Sn] ratio. From optical analysis, it is inferred that the band gap energy decreases from 1.83 to 1.77 eV when the [S]/[Sn] ratio changes from 2 to 4.     

In vivo proton magnetic resonance spectroscopy studies of human brain

In vivo localized proton magnetic resonance spectroscopy (MRS) studies of brain were performed on eighteen normal subjects using the stimulated echo (STE) sequence. The absolute concentrations and proton relaxation times of N-acetyl aspartate (NAA), total creatine (Cr) and choline (Cho) were estimated. The MRS data was quantitatively analyzed for repeatability and intersubject variability. Quantitative analysis indicates excellent spectral repeatability. Significant intersubject variations in [NAA] and [Cr] have been observed while the intersubject variability in [Cho] has been found to be fairly small. Significant intensity distortions have been observed for mixing times longer than 50 msec.     

Metabolite mapping of human filarial parasite, Brugia malayi with nuclear magnetic resonance

Metabolite mapping of human filarial parasite, Brugia malayi was carried out in vitro as well as in situ in host Mastomys coucha by ³¹P nuclear magnetic resonance (NMR) spectroscopy. Detection of parasites by visualizing contrast spots due to pathologic changes was observed by ¹H magnetic resonance imaging (MRI). Major metabolites of adult B. malayi observed by ³¹P-NMR spectroscopy were of sugar phosphates (SP), phosphomonoesters (PME), glycerophosphoryl-ethanolamine (GPE), -choline (GPC), phosphoenolpyruvate (PEP), inorganic phosphate (Pi), nucleoside diphosphosugar and nucleotides-mono, -di and -tri phosphates. PEP and GPC were present in high concentration; PEP being the major energy reservoir and GPC the major phospholipid in this species of filaria. The ³¹P NMR spectra of testis of mastomys, showed seven major peaks of SP, PME, phosphocreatine (PCr), phosphodiesters (PDE), Pi, and nucleotides di- and tri-phosphates. The ³¹P-NMR spectra of testis of B. malayi infected animal also consisted of seven major peaks with significant decrease in the SP and PME peak showing changes in the carbohydrate and lipid metabolism of filaria infected testis. Thus, in vivo ³¹P MRS provided a non-invasive assessment of tissue bioenergetics and phospholipid metabolism.     

鼠S180肉瘤的体内31P MRS研究

利用表面线圈³¹P NMR研究了小鼠S180肉瘤生长过程中能量代谢和磷脂类变化的特点.结果发现:随着肿瘤体积的增大,(1)Pi和PME升高;(2)PCr降低,在肿瘤体积较大时常检测不到;(3)β-NTP(通常用来表示ATP的量)变化较小;(4)PDE波动性较大;(5)PCr/Pi和β-NTP/Pi比值均下降,且PCr/Pi比β-NTP/Pi下降得快;(6)PME/β-NTP比值升高;(7)肿瘤pH下降,且与PCr/Pi、β-NTP/Pi或(PCr+β-NTP)/Pi比值有相关性.讨论了与这些参数变化相关联的生物学意义.     

Characterization of gallium-doped CdS thin films grown by chemical bath deposition

Ga-doped CdS thin films, with different [Ga]/[Cd] ratios, were grown using chemical bath deposition. The effect of Ga-doping on optical properties and bandgap of CdS films is investigated. Resistivity, carrier density, and mobility of doped films were acquired using Hall effect measurements. Crystal structure as well as crystal quality and phase transition were determined using X-ray diffraction (XRD) and Micro-Raman spectroscopy. Film morphology was studied using scanning electron microscopy, while film chemistry and binding states were studied using X-ray photoelectron spectroscopy (XPS). A minimum bandgap of 2.26 eV was obtained at [Ga]/[Cd] ratio of 1.7 × 10⁻². XRD studies showed Ga³⁺ ions entering the lattice substitutionally at low concentration, and interstitially at high concentration. Phase transition, due to annealing, as well as induced lattice defects, due to doping, were detected by Micro-Raman spectroscopy. The highest carrier density and lowest resistivity were obtained at [Ga]/[Cd] ratio of 3.4 × 10⁻². XPS measurements detect an increase in sulfur deficiency in doped films.