An image-based notion for therapeuticplanar organ activity dosimetry in a developing country: Masterdose software.

OBJECTIVE: Planar dosimetry is often performed in developing countries due to its simplicity during basic quantitative dosimetry. The geometric mean method is often used during planar dosimetry and imaging counts can be corrected for background, attenuation and scatter. The aim of our study was to develop computerized software called Masterdose that may be used for therapeutic isotope planar organ personalized dosimetry. MATERIALS AND METHODS: Masterdose software uses various methods to correct for background, scatter and attenuation.We also introduced a method to convert imaging counts to activity on the software,which is Java based and runs on Windows, Linux and Macintosh platforms. RESULTS: Three user interfaces named image processing, quantification and dosimetry were developed for the software. Masterdose could quantify kidney and liver doses of lutetium-177-DOTA-0-Tyr3-octreotate (177Lu-DOTATATE) patients. The software was validated throughcalculation of the kidney and liver doses of ten neuroendocrine tumour patients (NET) treated with 177Lu-DOTATATE. CONCLUSION: Masterdose presents an option for planar quantification that can be used as a quality control tool to verify imaging counts and perform dosimetry in particular organs.

The role of F-18 FDG PET/CT in evaluating the impact of HIV infection on tumor burden and therapy outcome in patients with Hodgkin lymphoma.

BACKGROUND: To evaluate the impact of HIV infection on tumor burden and therapy outcome following treatment with chemotherapy in patients with Hodgkin lymphoma. METHODS: A total of 136 patients with classical Hodgkin lymphoma were studied (mean age ± SD = 32.31 ± 1.39 years, male = 86, female = 50). Advanced disease (stage III and IV) was present in 64% of patients. HIV infection was present in 57 patients while 79 patients were HIV-negative. Baseline F-18 FDG PET/CT was obtained in all patients. SUVmax, MTV and TLG were determined on the baseline scan to evaluate for tumor burden. All patients completed a standard regimen of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). After a median period of 8 weeks (range = 6 to 17 weeks), a repeat F-18 FDG PET/CT scan was obtained to evaluate response to therapy using Deauville 5-point scoring system. RESULTS: The HIV-positive and HIV-negative groups were similar with regards to age and disease stage. The groups were heterogeneous with respect to gender (p = 0.029). The SUVmax, MTV and TLG of lesions were not significant different between the two groups. Complete response was seen in 72.8% of the study population. Presence of HIV infection was associated with higher rate of treatment failure with 40.4% of the HIV-positive patients having treatment failure while only 17.7% of the HIV-negative patients had treatment failure (p = 0.0034). HIV infection was a significant predictor of response to chemotherapy. Effects of SUVmax, MTV, TLG and Ann Arbor stage of the disease were not statistically significant as predictors of therapy outcome. In a multiple logistic regression, presence of HIV infection still remained an independent predictor of therapy outcome in the presence of other factors such as SUVmax, MTV, TLG and the Ann Arbor stage of the disease. CONCLUSIONS: HIV infection is not associated with a higher tumor burden in patients with Hodgkin lymphoma. HIV infection is, however, a strong predictor of poor therapy outcome in patients treated with standard regimen of ABVD.

A Comparison of 68Ga-PSMA PET/CT-Based Split Renal Function with 99mTc-MAG3 Renography in Patients with Metastatic Castration-Resistant Prostate Carcinoma Treated with 177Lu-PSMA.

BACKGROUND: Physiological PSMA expression in the cells of the proximal renal tubules and consecutive radiopharmaceutical binding and retention could potentially lead to radioligand-therapy-induced nephrotoxicity. Thus, patients with metastatic castration-resistant prostate cancer undergo 99mTc-Mercaptoacetyltriglycine (MAG3) renal scintigraphy to assess kidney function and to exclude renal obstruction as part of their workup for PSMA-targeted radioligand therapy (RLT). 99mTc-MAG-3 renal scintigraphy often requires an additional visit to the nuclear medicine department and patients spend 30-90 min in the department, which is inconvenient and takes up camera time. In addition, the patients are subjected to a baseline 68Ga-PSMA PET/CT to assess for PSMA-positive disease prior to targeted radioligand therapy. The aim of this retrospective cross-sectional study was to compare 99mTc-MAG-3-based split renal function (SRF) with 68Ga-PSMA-derived SRF. METHODS: This retrospective cross-sectional study included 28 patients with histologically proven metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA617. A comparison between the split renal function using 68Ga-PSMA PET/CT and the 99mTc-MAG-3-derived split renal function was carried out in 56 kidneys (n = 56). The SRF on 68Ga-PSMA was calculated using the volume and the average standard uptake value (SUVmean) within each VOI calculated as previously described by Roser et al.: SRF = (VOLUMEright) ∗ SUVmeanright/(VOLUMEright ∗ SUVmeanright + VOLUMEleft ∗ SUVmeanleft). Paired tests and correlation coefficients were used to compare 68Ga-PSMA and 99mTc-MAG-3. A visual comparison of kidney morphology on both studies was also performed. RESULTS: The median SRF of the right kidney was 49.9% (range: 3-91%) using 68Ga-PSMA PET/CT and 50.5% (range: 0-94%) with 99mTc-MAG3 scintigraphy. Notably, there was a strong correlation between SRF measurements obtained from PSMA and 99mTcMAG3, with a Pearson correlation coefficient of 0.957 (p < 0.001). Both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities; there were nine hydronephrotic kidneys, four shrunken kidneys and one obstructed kidney, and there was a strong positive correlation between 68Ga-PSMA kidney morphology and 99mTcMAG3 renal scintigraphy kidney morphology, with a correlation coefficient of 0.93. CONCLUSIONS: PSMA-derived split function demonstrated a high correlation with renal function assessed on diuretic 99mTc-MAG3 renograms. PET-derived split renal function may, therefore, be considered an alternative to diuretic renogram-based split function. Furthermore, both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities such as hydronephrosis, shrunken and obstructed kidneys. This correlation underscores the potential utility of 68Ga-PSMA imaging as a valuable tool for assessing kidney morphology as an alternative to renogram split function in clinical practice.

Chemokine Receptor-4 Targeted PET/CT Imaging with 68Ga-Pentixafor in Head and Neck Cancer-A Comparison with 18F-FDG and CXCR4 Immunohistochemistry.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is common, and its incidence is increasing, particularly in HIV-infected individuals who present with more aggressive disease. Despite aggressive treatment, the prognosis remains poor because of resistance to chemoradiation therapy. So far, studies report very low [68Ga]Ga-Pentixafor avidity in HNSCC. This study investigated the diagnostic performance of CXCR4-directed imaging of carcinoma of the oral cavity, oropharynx, and nasopharynx with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine ligand [68Ga]Ga-Pentixafor and explored its ability to quantify CXCR4 expression in vivo. MATERIALS AND METHODS: In this prospective cross-sectional study, twenty-three (23) patients aged 52.9 ± 10.4 (19.6), 17 males and 6 females with primarily diagnosed (n = 17) or pre-treated (n = 6) SCC of the oral cavity (OCSCC, n = 11), oropharynx (OPSCC, n = 9), nasopharynx (NPSCC, n = 2) and unknown primary (n = 1) underwent imaging with [68Ga]Ga-Pentixafor-PET/CT. In 16/23 patients 2-[18F]fluoro-2-deoxy-D-glucose ([18F]F-FDG) served as a standard reference. All lesions were visually rated using a 5-point Likert scale. For both tracers, maximum standardized uptake values (SUVmax) and the total lesion uptake (TLU) were recorded and compared using the Wilcox-signed rank test. In addition, the tumor-to-background ratios were derived using the liver (TLR), spleen (TSR), and posterior cervical muscles (TMR) as background. The relationships between the SUVs of the two tracers were assessed using the Spearman correlation. CXCR4 immunohistochemistry (IHC) staining was correlated with 68Ga-Pentixafor-PET/CT in 21/23 patients. RESULTS: Ninety-one percent (21/23) of tumors were visually detected on [68Ga]Ga-Pentixafor; however, [68Ga]Ga-Pentixafor was less intense compared with [18F]F-FDG-PET. Quantitative analysis showed higher [18F]F-FDG SUVmax in comparison with [68Ga]Ga-Pentixafor (16 ± 6.7 vs. 5.8 ± 2.6 g/mL, p = 0.011) and SUVmean (9.3 ± 4.1 vs. 3± 1.6 g/mL, p < 0.001) and TBR 4.9 ± 2.3 vs. 2.36 ± 1.4 p = 0.014. Nasopharyngeal cancer demonstrated more intense tracer accumulation than oropharyngeal and oral cavity malignancies. CXCR4 IHC staining was positive in 15/21 patients, and there was a statistically significant correlation between IHC staining and [68Ga]Ga-Pentixafor SUVmean r = 0.5 p = 0.027, and performance status r = 0.83 p = 0.0104. CONCLUSIONS: In conclusion, although [68Ga]Ga-Pentixafor cannot replace [18F]F-FDG as a diagnostic tool because of its lower avidity, the correlation between CXCR4 targeted 68Ga-Pentixafor PET imaging and CXCR4 IHC staining indicates the potential of 68Ga-Pentixafor as an effective tool for selecting patients who may benefit from therapies targeting CXCR4. In addition, [68Ga]Ga-Pentixafor has no physiological brown fat uptake, which often obscures cervical lesions on [18F]F-FDG PET/CT imaging.

Update on PET Radiopharmaceuticals for Imaging Hepatocellular Carcinoma.

Numerous positron emission tomography (PET) targets for detection and staging of hepatocellular cancer have been developed in recent years. Hepatocellular carcinomas (HCCs) are clinically and pathologically heterogeneous tumours with a high tendency to be aggressive and unresponsive to chemotherapy. Early detection is essential, and the need for an adequate imaging biomarker, which can overcome some of the limitations of conventional radiological imaging, is persistent. Flourine-18 (18F) flourodeoxyglucose (FDG), the most widely used PET radiopharmaceutical, has proven disappointing as a possible staple in the evaluation of HCC. This disappointment had led to experimentation with carious radiotracers, such as the choline derivatives, acetate, and prostate-specific membrane antigen, which appear to complement and/or enhance the role of FDG. In this study, we look at the various PET radiopharmaceuticals that have been used for imaging HCC and the particular pathways that they target in HCC and liver cancers.

The effectiveness of radionuclide scintigraphy in confirming testicular torsion at delayed presentation.

Background: Testicular torsion (TT) is a urological emergency that needs early diagnosis and intervention to prevent testicular death and necrosis. This study aimed to determine the efficacy of testicular scintigraphy (TS) in confirming the clinical diagnosis of TT and how this imaging method correlates with the surgical findings. Methods: A retrospective cohort review of clinical data was performed for 68 patients referred for TS from January 2016 to December 2021 to rule out possible TT. The final diagnosis was confirmed at surgery for all those with TS positive for TT. Results: The median age of the patients was 18.5 years, interquartile range of 15-31 years. Commonly presenting symptoms were pain (99%) and swelling (68%). Only 6% had history of trauma. TT was diagnosed by technetium-99m (99mTc)-pertechnetate in 35 (51%) patients all of whom underwent surgical exploration. Of this group, 7 (20%) had manual detorsion intraoperatively (intermittent torsion), in 20 (57%) missed (complete) torsion was confirmed and 8 (23%) had a necrotic testis. Of the remaining 33 patients with results negative for torsion, 10 were normal and 23 were diagnosed with either epididymitis 13/23 (57%), orchitis 3/23 (13%) or 7/23 (30%) with epididymo-orchitis. TT was more common in patients under 15 and 15-19 years (P<0.05). The mean presentation time was 5 days with a range of 1-30 days. Conclusions: The 99mTc-pertechnetate scan remains an effective investigation in the diagnosis of TT and may serve as a gate-keeper for surgery even in patients who present late for treatment.

Utility of 18F FDG-PET in Parkinsonism in an African population.

Parkinson's Disease remains a diagnostic challenge. Misdiagnosis during life is approximately 25%. Diseases that resemble PD clinically, such as the Parkinsonianplus disorders usually have a poorer prognosis. A diagnostic biomarker is needed to differentiate PD from PPS. Geographical differences in PD prevalence, genetics and environmental factors may suggest a different pathogenesis of PD in Africa which may affect metabolic changes seen on 18F-FDG-PET. We investigated the utility of 18FFDG-PET in differentiating PD from PPS in a real-life clinical setting. The study was conducted at the Movement Disorder Clinic, South Africa. 81 patients with Parkinsonism had fluorine-18-labelled-fluorodeoxyglucose-PET; 53 PD and 28 PPS. Six persons living with HIV and Parkinsonism were included. Of the 22 Black African patients, 21 had PD and only one had a PPS. Image-based diagnosis was made by visual interpretation aided by statistical parametric mapping (SPM) analysis by a Nuclear Medicine Physician blinded to the clinical diagnosis. This was compared to the final clinical diagnosis made by two Movement disorder Neurologists blinded to the 18F-FDG-PET diagnosis. Patients were followed up for a median of 4 years. 18F-FDGPET diagnosis was in agreement with final clinical diagnosis in 91% of all subjects (90% PD, 93% all PPS). Our paper reports the clinically realistic sample of patients seen with Parkinsonism in Africa. The present data shows that 18F-FDG-PET can distinguish PD from PPS with good accuracy. Few Black Africans present with an Atypical Parkinsonian syndrome. The pattern of metabolism in PLH-PD is similar to PD patients without HIV.

Segmented linear correlations between bone scan index and prostate cancer biomarkers, alkaline phosphatase, and prostate specific antigen in patients with a Gleason score ≥7.

ABSTRACT: Technetium-99m methyl diphosphonate bone scintigraphy is relatively easily accessible for detecting bone metastases in prostate cancer patients. However, it is subjective and can be challenging to compare images taken at different time points. The bone scan index (BSI) is a more objective evaluation and allows for better comparison of images. Its correlation with other biomarkers of prostate cancer metastases such as prostate specific antigen (PSA) and alkaline phosphatase (ALP) is not clearly understood. This study thus aimed to compare the BSI correlation to PSA against that of BSI to ALP levels in patients with a Gleason score ≥7.A retrospective analysis of the medical records of 50 prostate cancer patients with a Gleason score of ≥7 referred for a bone scan between January 1, 2015 and December 31, 2018 was undertaken. Bone scans were interpreted visually, and using a semi-automated computer programme to quantify the BSI and its relation to PSA and ALP measurements.For the metastasis positive measurements, there was a statistically significant moderate positive overall linear correlation between BSI and PSA. For ALP and BSI, there were 2 segmented strong positive linear relationships between them. The first segment consisted of ALP < 375 IU/L and BSI >10%, where ALP and BSI were strongly and positively correlated. The other segment tended to have generally low BSI measurements (<10%) and also had a strong and positive correlation.The BSI was found to be better linearly correlated with ALP than PSA.

Critical Appraisal of Radionuclide Calibrators and Gamma Cameras Prior to Lutetium-177 Internal Dosimetry at Two South African Hospitals.

Introduction The functionality of radionuclide dose calibrator and nuclear medicine imaging systems hasa direct effect on the accuracy and preciseness of internal dosimetry evaluations. Our study, therefore, aimed to critically appraise the radionuclide calibrators and gamma cameras prior to Lutetium-177 ( 177 Lu) internal dosimetry in a developing country. Materials and Methods Two radionuclide calibrators' and three gamma cameras at two South African hospitals were critically appraised in preparation for internal dosimetry of 177 Lu. The radionuclide calibrators' accuracy, linearity, and sample volume abilities were appraised. For the three gamma cameras, the uniformity, energy resolution, center of rotation, and collimator sensitivity were appraised. These appraisals were performed between the years 2014 and 2019. Results The radionuclide calibrators' constancy, accuracy, linearity, and sample volume were within ± 5%. We also integrated a 177 Lu calibration factor into one radionuclide calibrator's library. The three gamma cameras' uniformity was within 2 to 5%, energy resolution within 11%, center of rotation within 2 mm, and the sensitivity recorded for all low energy high resolution collimator. Conclusion Our radionuclide calibrators passed the critical appraisal and may be confidently used for assaying 177 Lu. All three cameras also passed critical appraisal and may be used to assess organ absorbed dose.

Comparing 99mTc-PSMA to 99mTc-MDP in Prostate Cancer Staging of the Skeletal System.

PURPOSE: This prospective study was aimed at assessing the ability of 99mTc-PSMA scan to detect bone metastases in prostate cancer (PCa) against 99mTc-MDP scan as a standard and assess the correlation of these modalities in PCa staging of bone involvement. PATIENTS AND METHODS: Forty-one patients (41) with histologically confirmed PCa were scanned using both methods. Planar imaging was performed with additional regional SPECT/CT 3 to 4 hours posttracer injection. Scans were reported as positive, negative, or equivocal. In the case of positive scans, lesions were quantified by each of the 3 reporters separately. Planar and SPECT/CT images were reported together to obtain the final report on each scan. RESULTS: Our preliminary results showed no significant difference in the detection of bone metastases between the 2 scans. 99mTc-PSMA detected 52 of the 55 bone lesions detected on 99mTc-MDP. However, 99mTc-PSMA provided extra information by reporting lymph nodal metastases in 7 patients and residual disease in the prostate in 2 patients with biochemical progression after radical therapy. In 1 patient, the PSMA scan resulted in change in management with patient now on 177Lu-PSMA radioligand therapy. Equivocal findings were reported in 4 patients on 99mTc-MDP and none on 99mTc-PSMA. CONCLUSIONS: 99mTc-PSMA was comparable to 99mTc-MDP in detection of bone metastases and demonstrated an additional benefit of providing information on visceral disease. 99mTc-PSMA may be a better alternative to 99mTc-MDP in staging, restaging, and assessment of patients with biochemical progression after radical therapy of PCa in a resource-limited setup like ours while also assisting to detect patients eligible for PSMA-labeled radioligand therapy.

Metastatic Papillary Thyroid Carcinoma in a Paediatric Patient.

Papillary thyroid carcinoma is the most common endocrine cancer in the paediatric population. Although the disease is diagnosed at a later stage, the prognosis is favourable. When these patients present with lymph nodal and/or pulmonary metastases, they may be initially confused for infectious diseases such as tuberculosis. Therefore, thorough clinical assessment including radiology and microbiological and histopathological assessment is important for early and correct diagnosis. We report an 11-year-old female patient who presented with cervical lymphadenopathy and the histopathological assessment confirmed metastatic papillary thyroid carcinoma. Subsequent radiological investigation revealed further metastasis to the lung. This manuscript highlights the difficulties that might be encountered in the initial management of paediatric PTC which present atypically.

Scintigraphic peritoneography in the diagnosis of pleuroperitoneal leak complicating peritoneal dialysis: A comparison with conventional diagnostic methods.

A pleuroperitoneal leak (PPL) is a relatively rare complication of peritoneal dialysis (PD) and early diagnosis is essential.Patients suspected of a PPL usually present with dyspnea (marked during inflow of PD fluid) and tend to have transudative high glucose pleural effusions.The PPL scintigraphy (PPLS) is one of the methods for objectively proving a PPL. The effectiveness of PPLS as a noninvasive method of evaluating a suspected PPL and its effectiveness in the exclusion of a leak in patients with similarly presenting comorbidities was assessed.Patients suspected to have a PPL were considered for PPLS based on clinical presentation and pleural fluid analysis. Radiopharmaceutical was administered into the peritoneum via the dialysis port with the patient lying supine and immediate dynamic followed by delayed statics were acquired.Of the 27 scans reviewed, 70% were found to be positive with majority detected within 12 minutes of radiopharmaceutical administration with a high predominance occurring in the right chest (P < .001). In PPLS-positive patients, when both chest X-rays and planar agreed on showing the right-sided chest predominance, the highest measurements of the pleural glucose:serum glucose ratio were recorded. A statistically significant correlation between the outcome of the scan and final decision on patient management was noted (P < .01).The PPLS is an effective diagnostic tool for assessing PPLS. However, multicenter studies investigating its added value over other conventional methods are needed to establish it as a highly relevant diagnostic tool.

18F-FDG-PET metabolic metrics and International Prognostic Score for risk assessment in HIV-infected patients with Hodgkin lymphoma.

OBJECTIVES: Baseline metabolic metrics on fluorine-18-fluorodeoxyglucose PET (F-FDG PET) have prognostic value in Hodgkin lymphoma. International Prognostic Score (IPS) is used in the risk stratification of Hodgkin lymphoma. We compared the metabolic indices in HIV-infected and the IPS in HIV-infected and uninfected patients with Hodgkin lymphoma. PATIENTS AND METHODS: We retrospectively reviewed the data of HIV-infected and HIV-uninfected patients with classic Hodgkin lymphoma who had F-FDG PET for staging and compared the maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume, and total lesion glycolysis between the two groups. We also compared the IPS and other prognostic indicators and correlated them with the metabolic indices in the two groups. RESULTS: We studied 160 patients, which included 57 patients who were infected with HIV. The mean age was 33.84±11.88 years, with 38% (n=61) being female. The median cluster of differentiation 4 count and HIV viral load were 259 cells/mm and 4837.50 copies/ml, respectively. No significant difference in maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume, and total lesion glycolysis between the two groups was found. Among the seven parameters of the IPS, only male sex (HIV-uninfected group higher, P=0.005) and serum albumin less than 4 g/dl were significantly different. The other parameters were not significantly different between the two groups. Other prognostic indicators including bulky disease, extranodal involvement, and the number of nodal groups involved were not significantly different between the two groups. CONCLUSION: There was no significant difference in F-FDG metabolic parameters, IPS, and other risk indicators between HIV-infected and HIV-uninfected patients with Hodgkin lymphoma.

Higher preablative serum thyroid-stimulating hormone level predicts radioiodine ablation effectiveness in patients with differentiated thyroid carcinoma.

INTRODUCTION: Radioiodine ablation of remnant thyroid tissue is an important adjuvant therapy of differentiated thyroid carcinoma (DTC) after thyroidectomy. Elevated serum thyroid-stimulating hormone (TSH) level is necessary for successful ablation. The optimum level of serum TSH level necessary for successful radioiodine ablation of well-DTC is, however, yet to be defined. We aimed to determine whether higher serum TSH level will result in a better rate of complete ablation of well-DTC using iodine-131 (I) following initial thyroidectomy. PATIENTS AND METHODS: A total of 109 patients with differentiated thyroid cancer were divided into four treatment groups on the basis of serum TSH levels. They were followed up from 6 to 12 months after treatment with stimulated serum thyroglobulin level and a diagnostic whole-body scan with radioactive iodine I to determine early response. RESULTS: Sixty-four patients had papillary thyroid carcinoma, whereas 45 patients had follicular carcinoma. An excellent response was observed in 66.7% of patients with TSH level more than 90 µIU/ml, 72.2% in the group with TSH level of 60-89 µIU/ml, 48.5% when TSH was 30-59 µIU/ml and 26.7% when TSH was less than 30 µIU/ml (P=0.002). CONCLUSION: Higher preablative serum TSH predicts a better rate of ablation in patients with differentiated thyroid cancer treated with I after thyroidectomy.

Appropriate indications for positron emission tomography/computed tomography, 2015.

These recommendations are intended to serve an important and relevant role in advising referring physicians on the appropriate use of 18F-fluorodeoxyglucose (18F-FDG) and non-18F-FDG positron emission tomography/computed tomography (PET/CT), which can be a powerful tool in patient management in oncology, cardiology, neurology and infection/inflammation. PET is a non-invasive molecular imaging tool that provides tomographic images and quantitative parameters of perfusion, cell viability, proliferation and/or metabolic activity of tissues. These images result from the use of different substances of biological interest (sugars, amino acids, metabolic precursors, hormones) labelled with positron-emitting radionuclides (PET radiopharmaceuticals). Fusion of the aforementioned important functional information with the morphological detail provided by CT as PET/CT provides clinicians with a sensitive and accurate one-step whole-body diagnostic and prognostic tool, which directs and changes patient management. Hence PET/CT is currently the most widely used molecular imaging technology for a patient-tailored treatment approach. In these recommendations we outline which oncological and non-oncological indications are appropriate for PET/CT. Once each combination of pathology and clinical indication is defined, a recommendation is given as: 1. Recommended; 2. Recommended in select cases; 3. May be considered; or 4. Not recommended.

Clinical and brain SPECT scan response to zolpidem in patients after brain damage.

UNLABELLED: Previous reports document transient improvements after daily zolpidem (CAS 82626-48-0) in patients with brain damage. This multi-patient study evaluates the response to zolpidem in neurologically disabled patients, using 99mTcHMPAO brain SPECT scans and clinical rating scales. METHOD: 23 of 41 consecutive adult patients, at least 6 months after brain damage were identified as neurologically disabled patients by scoring less than 100/100 on the Barthel Index. Causes of their brain damage included stroke (n = 12), traumatic brain injury (n = 7), anaphylaxis (n = 2), drugs overdose (n = 1) and birth injury (n = 1). The selected 23 patients had a baseline 99mTcHMPAO brain SPECT scan before starting daily zolpidem therapy and a second within two weeks of therapy, performed 1 h after 10 mg oral zolpidem. Scans were designated as improved when at least two of three assessors detected improvement after zolpidem. The rest were designated non improved. After four months daily zolpidem therapy, patients were rated on the Tinetti Falls Efficacy Scale (TFES) before and after zolpidem. The TFES ratings were compared using a Wilcoxon non parametric signed rank test. Scan improvers were compared with non improvers, using a two sample t test with unequal variance. RESULTS: Mean overall improvement after zolpidem on TFES was 11.3%, from 73.4/100 to 62.1/100 (p = 0.0001). 10/23 (43%) patients improved on SPECT scan after zolpidem. Their mean TFES improvement was 19.4% (+/- 16.75) compared with 5.08% (+/- 5.17) in 13/23 non improvers (p = 0.0081). CONCLUSION: This prospective study adds further evidence to previous reports of zolpidem efficacy in patients with established brain damage.