Resilience-enhancing interventions for family caregivers: A systematic review.

OBJECTIVES: To synthesize interventions designed to enhance resilience in family caregivers (FCs). METHODS: Electronic databases including PubMed, CINAHL, PsycINFO, and Scopus, were searched using index and keyword methods for articles published before January 2020. The review process followed the PRISMA review guidelines. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Six studies (seven articles) were included in this review. Quantitative evidence supports the benefits of psychoeducation, mindfulness-based intervention, and cognitive behavioral therapy (CBT)-based intervention but not expressive writing in improving in FCs' resilience. Four of the six included studies were randomized controlled trials. All included studies only met 40% to 60% of the MMAT criteria, indicating low to moderate levels of study quality. CONCLUSION: This review showed emerging evidence that psychoeducation, mindfulness-based intervention, and CBT-based intervention may improve caregiver resilience. However, it remains unclear which intervention and what dosage is the most effective in promoting FCs' resilience. Due to the small number of relevant studies and a low-to-moderate level of overall study quality, more rigorous clinical trials are needed to strengthen the current limited evidence base for FC resilience interventions.

Family Caregiver Challenges in Pain Management for Patients with Advanced Illnesses: A Systematic Review.

Although pain management is integral to the caregiving role, there is a paucity of evidence synthesizing specific challenges family caregivers (FCs) face when managing pain for their care partners. This review comprehensively identified and summarized such challenges in the setting of advanced illnesses. Electronic databases (PubMed, CINAHL, PsycINFO, Scopus, and Health and Psychosocial Instruments) were searched using index and keyword methods for all articles published before April 2021. Fifty-five studies were included in this review. Most articles were published within the last 10 years (54%) in community settings, with home hospice care comprising the majority (50%). Most studies included patients with an advanced cancer diagnosis (84%), and 16% of the studies included patients with a noncancer diagnosis. Four major categories of challenges were identified: (1) caregiver-related issues (e.g., fears, beliefs, function), (2) caregivers' limited knowledge and skills in pain management (e.g., verbal and nonverbal pain assessment skills, pharmacological knowledge, documentation, safe management of medication), (3) communication challenges with health care providers, and (4) patient-related issues (e.g., inability to report pain). Many of these challenges have not been fully addressed in prior literature. Thus, this review provides a framework for needed future research to develop interventions that target FCs' specific challenges in providing pain management. The results also highlight a significant lack of research surrounding challenges faced by caregivers of care partners having a noncancer, dementia, or multimorbidity diagnosis.

Interventions to Support Family Caregivers in Pain Management: A Systematic Review.

CONTEXT: Family caregivers encounter many challenges when managing pain for their loved ones. There is a lack of clear recommendations on how to prepare caregivers in pain management. OBJECTIVES: To evaluate existing interventions that support family caregivers in providing pain management to patients with all disease types. METHODS: Four electronic databases were systematically searched (PubMed, Cumulative Index for Nursing Allied Health Literature, PsycINFO, and Scopus) using index and keyword methods for articles published before December 2019. The Mixed Methods Appraisal Tool was used to assess the quality. RESULTS: The search identified 6851 studies, and 25 studies met the inclusion criteria. Only two studies exclusively focused on noncancer populations (8%). Three types of interventions were identified in this review: educational interventions, cognitive-behavioral interventions, and technology-based interventions. Both educational and cognitive-behavioral interventions improved family caregiver and patient outcomes, but the content and intensity of these interventions in these studies varied widely, and there was a limited number of randomized clinical trials (68%). Hence, it is unclear what strategies are most effective to prepare family caregivers in pain management. Technology-based interventions were feasible to support family caregivers in providing pain management. CONCLUSION: Providing adequate pain management training can improve patient and family caregiver outcomes. However, the most effective interventions for family caregivers are still unclear. More rigorous and replicable clinical trials are needed to examine the effects of educational interventions, cognitive-behavioral interventions, and technology-based interventions. Also, more studies are needed in patients with a noncancer diagnosis or multimorbidity.

The role of molecular imaging in the diagnosis and management of neuropsychiatric disorders.

Neuropsychiatric disorders are becoming a major socioeconomic burden to modern society. In recent years, a dramatic expansion of tools has facilitated the study of the molecular basis of neuropsychiatric disorders. Molecular imaging has enabled the noninvasive characterization and quantification of biological processes at the cellular, tissue, and organism levels in intact living subjects. This technology has revolutionized the practice of medicine and has become critical to quality health care. New advances in research on molecular imaging hold promise for personalized medicine in neuropsychiatric disorders, with adjusted therapeutic doses, predictable responses, reduced adverse drug reactions, early diagnosis, and personal health planning. In this paper, we discuss the development of radiotracers for imaging dopaminergic, serotonergic, and noradrenergic systems and ß-amyloid plaques. We will underline the role of molecular imaging technologies in various neuropsychiatric disorders, describe their unique strengths and limitations, and suggest future directions in the diagnosis and management of neuropsychiatric disorders.

Identification of a new peptide for fibrosarcoma tumor targeting and imaging in vivo.

A 12-mer amino acid peptide SATTHYRLQAAN, denominated TK4, was isolated from a phage-display library with fibrosarcoma tumor-binding activity. In vivo biodistribution analysis of TK4-displaying phage showed a significant increased phage titer in implanted tumor up to 10-fold in comparison with normal tissues after systemic administration in mouse. Competition assay confirmed that the binding of TK4-phage to tumor cells depends on the TK4 peptide. Intravenous injection of (131)I-labeled synthetic TK4 peptide in mice showed a tumor retention of 3.3% and 2.7% ID/g at 1- and 4-hour postinjection, respectively. Tumor-to-muscle ratio was 1.1, 5.7, and 3.2 at 1-, 4-, and 24-hour, respectively, and tumors were imaged on a digital γ-camera at 4-hour postinjection. The present data suggest that TK4 holds promise as a lead structure for tumor targeting, and it could be further applied in the development of diagnostic or therapeutic agent.

Multimodality imaging and preclinical evaluation of 177Lu-AMBA for human prostate tumours in a murine model.

AMBA (DO3A-CH(2)CO-G-(4-aminobenzoyl)-QWAVGHLM-NH(2)) is a bombesin (BN)-like peptide having high affinity with gastrin-releasing peptide receptors (GRPr).(177)Lu-AMBA is currently undergoing clinical trial as a systemic radiotherapy for hormone refractory prostate cancer (HRPC) patients. This study evaluated the biodistribution, pharmacokinetics, bioluminescent imaging (BLI) and microSPECT/CT imaging of (177)Lu-AMBA in PC-3M-luc-C6 luciferase-expressing human prostate tumour-bearing mice. Plasma stability of (177)Lu-AMBA could be maintained up to 55.67±6.07% at 24 h in a protection buffer. High positive correlations of PC-3M luc-C6 tumour growth in SCID mice between caliper measurement and BLI were observed (R(2)=0.999). Both the biodistribution and microSPECT/CT imaging in PC-3M-luc-C6 bearing-tumour mice showed that (177)Lu-AMBA in tumour uptake could be retained for 24 h. The distribution half-life (t(1/2α)) and the elimination half-life (t(1/2ß)) of (177) Lu-AMBA in mice were 0.52 h and 26.6 h, respectively. These results indicated that BLI could be used to monitor the growth of tumour. High uptake of (177)Lu-AMBA in PC-3M-luc-C6 tumour-bearing mice by microSPECT/CT imaging can further evaluate the potential of (177)Lu-AMBA therapy for PC-3M-luc-C6 tumours.

Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys.

PURPOSE: 4-[(18)F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken. METHODS: Single and multiple-dosage toxicity studies were conducted in Sprague-Dawley rats. Male and female rats were injected intravenously with 4-F-ADAM as a single dose of 1,023.7 microg/kg (1,000 times the human dose) or as five consecutive daily doses of 102.37 microg/kg (100 times the human dose). PET/CT scans were performed in seven Formosa Rock monkeys (four males and three females) using a Siemens Biograph scanner. After injection of 4-[(18)F]-ADAM (182+/-8 MBq), a low dose CT scan and a series of eight whole-body PET scans were performed. Whole-body images were acquired in 3-D mode. Time-activity data of source organs were used to calculate the residence times and estimate the absorbed radiation dose using OLINDA/EXM software. RESULTS: In the rats neither the single dose nor the five daily doses of 4-F-ADAM produced overt adverse effects clinically. In the monkeys the radiation doses received by most organs ranged between 7.1 and 35.7 microGy/MBq, and the urinary bladder was considered to be the critical organ. The effective doses extrapolated to male and female adult humans were 17.4 and 21.8 microSv/MBq, respectively. CONCLUSION: Toxicity studies in Sprague-Dawley rats and radiation dosimetry studies in Formosa Rock monkeys suggested that 4-[(18)F]-ADAM is safe for use in human PET imaging studies.

Imaging of regional metabolic activity by (18)F-FDG/PET in rats with transient cerebral ischemia.

Changes in regional metabolic activities induced by middle cerebral artery occlusion (MCAO) can influence patient outcome. Our aim was to demonstrate in a rat model that (18)F-FDG with positron emission tomography (PET) imaging is a quantitative, reproducible approach for identifying acute and sub-acute metabolic variations in infarct regions. We found that imaging with (18)F-FDG/PET enabled detection and quantification of ischemia-induced metabolic deficits and provided a sensitive and reliable means of assessing cerebral ischemic lesions compared with conventional neurological scoring systems in rodents.

Imaging serotonin transporters using [123I]ADAM SPECT in a parkinsonian primate model.

Parkinson's disease (PD) affects multiple neurotransmitter systems. The purpose of this study was to investigate differences in the serotonin transport system between normal and parkinsonian monkeys using 2-([2-([di-methylamino]methyl)phenyl]thio)-5-[(123)I] iodophenyl-amine([(123)I]ADAM), a serotonin transporters (SERT) radioligand. The brain single photon emission computed tomography (SPECT) was performed on two normal and one parkinsonian monkey. The parkinsonian monkey was induced by bilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle under magnetic resonance imaging (MRI) guidance. Each monkey underwent two [(99m)Tc] TRODAT-1 (a dopamine transporters imaging agent) and two [(123)I] ADAM brain SPECT scans. After a bolus injection of the radioligand, the SPECT data were acquired over 4h using a dual-head gamma camera equipped with ultra-high resolution fan-beam collimators. The striatal uptake of [(99m)Tc]TRODAT-1 was 46% lower in the parkinsonian monkey than those of normal monkeys at 210-240 min post-injection. [(123)I]ADAM uptake in the midbrain of the parkinsonian monkey was comparable to those of the controls. The uptakes of [(123)I]ADAM in the striatum, thalamus, and frontal cortex of the parkinsonian monkey, were 31%, 31%, and 23% lower than those of normal monkeys at 210-240 min post-injection, respectively. Our results suggest that [(123)I]ADAM SPECT has potential for evaluating the serotonin transporter changes in human PD.

[99mTc]TRODAT-1/[123I]IBZM SPECT studies of the dopaminergic system in Tourette syndrome.

The good clinical effectiveness of dopamine depleter and receptor antagonists on tics suggests dopaminergic hyperactivity in Tourette syndrome (TS). In this case-control study of 10 TS patients and 15 age-matched healthy controls, we evaluated (i) presynaptic and postsynaptic striatal dopaminergic function using [(99m)Tc]TRODAT-1/[(123)I]IBZM single photon emission computed tomography (SPECT) and (ii) correlations between dopamine transporter (DAT)/D2 receptor binding sites and tic severity scores. Patients 1-5 were pretreated with haloperidol and were drug free for at least 3 months before SPECT imaging. Patients 6-10 were drug-naïve. We found no significant difference in DAT and D2 receptor binding sites between TS patients and healthy controls nor any association between striatal DAT or D2 receptor binding sites and tic severity assessed using the Modified Rush Videotape Rating Scale. Our findings provided no direct evidence of abnormally available striatal DAT or dopamine D2 receptors in TS. However, functional abnormalities of the dopaminergic system, e.g., alterations in the synaptic release of endogenous dopamine, cannot be completely ruled out.

Methylphenidate DAT binding in adolescents with Attention-Deficit/ Hyperactivity Disorder comorbid with Substance Use Disorder--a single photon emission computed tomography with [Tc(99m)]TRODAT-1 study.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent among adolescents with Substance Use Disorders (SUD). Effects of methylphenidate (MPH) on ADHD are attributed to its properties of blocking the dopamine transporter (DAT) in the striatum. However, it has been demonstrated that drug addiction is associated with dopaminergic system changes that may affect MPH brain effects, emphasizing the need to better understand MPH actions in subjects with ADHD+SUD. OBJECTIVES: To evaluate the effect of an extended release formulation of MPH (MPH-SODAS) on DAT availability in 17 stimulant-naive ADHD adolescents with comorbid SUD (cannabis and cocaine). METHODS: Subjects underwent two single photon emission computed tomography (SPECT) scans with [Tc(99m)]TRODAT-1, at baseline and after 3 weeks on MPH-SODAS. Clinical assessment for ADHD relied on the Swanson, Nolan and Pelham Scale - version IV (SNAP-IV). Caudate and putamen DAT binding potential (BP) was calculated. RESULTS: After 3 weeks on MPH-SODAS, there was a significant reduction of SNAP-IV total scores (p<0.001), and approximately 52% reductions of DAT BP at the left and right caudate. Similar decreases were found at the left and right putamen (p<0.001 for all analyses). DISCUSSION: This study shows that the magnitude of DAT blockade induced by MPH in this population is similar to what is found in ADHD patients without SUD comorbidity, providing neurobiological support for trials with stimulants in adolescents with ADHD+SUD, an important population excluded from studies.

Higher nigrostriatal dopamine neuron loss in early than late onset Parkinson's disease?--a [99mTc]-TRODAT-1 SPECT study.

Early-onset Parkinson's disease (EOPD) is distinct from the classic late-onset PD (LOPD) because of its slower disease progression. The aim of this study was to compare dopamine neuronal loss in EOPD with that of LOPD with the same disease duration, through dopamine transporter (DAT) estimation. Fourteen patients, seven EOPD (<50 years) and seven LOPD, matched for disease duration were scanned with [(99m)Tc]-TRODAT-1-SPECT (INER-Taiwan), and were assessed with standard PD scales. EOPD patients had 34% lower striatal DAT binding potential (BP) compared with that of LOPD patients (BP = 0.29 +/- 0.12, BP = 0.44 +/- 0.12, P < 0.02) with similar PD severity. These results suggest that EOPD patients have greater dopamine density loss than LOPD patients without motor-symptom worsening.

[Neuroimaging of the dopamine transporter in Parkinsons disease: first study using [99mTc]-TRODAT-1 and SPECT in Brazil]. / Neuroimagem do transportador de dopamina na doença de Parkinson: primeiro estudo com [99mTc]-TRODAT-1 e SPECT no Brasil.

BACKGROUND: Dopamine transporter (DAT) neuroimaging radiotracers were developed to estimate dopamine neuronal loss in vivo in Parkinsons disease (PD). OBJECTIVE: To evaluate DAT density in vivo using [99mTc]-TRODAT-1 and single photon computerized tomography (SPECT) in a population of Brazilian PD. METHOD: Fifteen PD patients and 15 matched healthy controls scanned with [99mTc]-TRODAT-1 (INER-Taiwan) and SPECT. Estimates of striatum DAT density were calculated using binding potential (BP). Patients were assessed with PD scales. RESULTS: PD patients had significantly lower striatal DAT-BP (mean+/-SD) (0.38+/-0.12) compared to controls (BP=0.84+/-0.16; p<0.01). A 100% sensitivity and 100% specificity was obtained to discriminate PD cases from controls. Negative correlations between striatal DAT-BP and PD severity (rho=-0.7, p<0.001) and motor scales (rho=-0.80, p<0.001) were found. CONCLUSION: [99mTc]TRODAT-1 SPECTs scanning was able to discriminate PD patients from controls. The technique is a powerful instrument to measure DAT density that can be used in clinical and research settings in Brazil.

Neuroimagem do transportador de dopamina na doença de Parkinson: primeiro estudo com [99mTc]-TRODAT-1 e SPECT no Brasil / Neuroimaging of the dopamine transporter in ParkinsonÆs disease: first study using [99mTc]-TRODAT-1 and SPECT in Brazil / Neuroimaging of the dopamine transporter in Parkinson's disease: first study using [99mTc]-TRODAT-1 and SPECT in Brazil

INTRODUÇÃO: Radiotraçadores para neuroimagem de transportador de dopamina (TDA) foram desenvolvidos para estimar a perda de neurônios dopaminérgicos in vivo na doença de Parkinson (DP). OBJETIVO: Avaliar a densidade de TDA in vivo utilizando [99mTc]-TRODAT-1 (INER-Taiwan) e SPECT em uma população de pacientes brasileiros com DP. MÉTODO: Quinze pacientes com DP e 15 controles saudáveis pareados realizaram exames de SPECT com [99mTc]-TRODAT-1 (INER-Taiwan). Estimativas da densidade de TDA estriatal foram calculadas usando potencial de ligação (PL). Pacientes foram avaliados com escalas para PD. RESULTADOS: Pacientes com DP apresentaram redução significativa do PL-TDA (0,38±0,12) comparado aos controles (0,84±0,16, p<0,01). Foi possível discriminar casos de DP de controles com uma sensibilidade de 100 por cento e especificidade de 100 por cento. Foram obtidas correlações negativas entre PL-TDA e escalas de severidade da DP (rho= -0,7, p<0,001) e disfunção motora (rho= -0,8, p<0,001). CONCLUSÃO: Exames de SPECT com [99mTc]-TRODAT-1 foram capazes de discriminar pacientes com DP de controles. Esta técnica é um instrumento útil para medir a densidade de TDA e pode ser utilizado para clínica e pesquisa no Brasil.

BACKGROUND: Dopamine transporter (DAT) neuroimaging radiotracers were developed to estimate dopamine neuronal loss in vivo in ParkinsonÆs disease (PD). OBJECTIVE: To evaluate DAT density in vivo using [99mTc]-TRODAT-1 and single photon computerized tomography (SPECT) in a population of Brazilian PD. METHOD: Fifteen PD patients and 15 matched healthy controls scanned with [99mTc]-TRODAT-1 (INER-Taiwan) and SPECT. Estimates of striatum DAT density were calculated using binding potential (BP). Patients were assessed with PD scales. RESULTS: PD patients had significantly lower striatal DAT-BP (mean±SD) (0.38±0.12) compared to controls (BP=0.84±0.16; p<0.01). A 100 percent sensitivity and 100 percent specificity was obtained to discriminate PD cases from controls. Negative correlations between striatal DAT-BP and PD severity (rho= -0.7, p<0.001) and motor scales (rho= -0.80, p<0.001) were found. CONCLUSION: [99mTc]TRODAT-1 SPECTs scanning was able to discriminate PD patients from controls. The technique is a powerful instrument to measure DAT density that can be used in clinical and research settings in Brazil.

Comparative evaluation of FET and FDG for differentiating lung carcinoma from inflammation in mice.

BACKGROUND: Clinical FDG/PET (2-deoxy-2-18F-fluoro-D-glucose/positron emission tomography) studies encounter difficulties in detecting early stage lung cancers. The aim of this study was to evaluate the ability of O-2-18F-fluoroethyl-L-tyrosine (FET) and FDG to differentiate between inflammation and lung carcinoma in mice. MATERIALS AND METHODS: Sixty-four C57BL/6 mice were inoculated with 2x10(6) LLC1 lung carcinoma cells in the right hind flank on day 0 and were then injected with 0.1 mL turpentine in the left thigh muscle on day 3. The progress of inflammation and tumor in mice was longitudinally monitored by FDG/microPET. The biodistribution study, pharmacokinetic evaluation and whole-body autoradiography of FET and FDG were performed on day 8 after tumor inoculation. RESULTS: The FDG uptakes in tumor and inflammatory lesions were 4.42-fold and 3.53-fold (n = 4) higher, respectively, than that in muscle at 90 min post-injection and the tumor-to-inflammation ratio was 1.25. For FET/microPET, the tumor uptake was 2.07-fold and 2.07-fold (n = 4) higher than those in muscle and inflammatory lesions at 90 min post-injection, respectively. The distribution half-life (t1/2,alpha) and the elimination half-life (t1/2,beta) of FET were 39 min and 205 min, respectively, in mice. CONCLUSION: FDG delineated both tumor and inflammation, while FET accumulated in tumor to a significantly higher extent. Our results demonstrated the potential of FET to distinguish epidermoid lung carcinoma from inflammatory lesions in mice.

Serial in vivo imaging of the lung metastases model and gene therapy using HSV1-tk and ganciclovir.

UNLABELLED: Noninvasive imaging in lung metastatic tumor models is used infrequently because of technical limitations in detecting metastases. We have previously used 2'-fluoro-2'-deoxy-5-iodo-1-beta-d-arabinofuranosyluracil labeled with (131)I ((131)I-FIAU) and demonstrated the applicability of noninvasive imaging for monitoring cancer gene therapy in an experimental animal model of herpes simplex virus type 1 thymidine kinase (HSV1-tk)-expressing tumor xenografts. We have now used the same animal model to effectively and noninvasively monitor the location, magnitude, and duration of therapeutic gene expression over time for the lung metastases model. METHODS: To improve the detectability of lung metastases, an experimental blood-borne lung metastases model in mice was established using intravenously administered HSV1-tk-expressing NG4TL4 fibrosarcoma cells (NG4TL4-TK) and simulated the clinical application of HSV1-tk plus ganciclovir (GCV) prodrug activation gene therapy. The efficacy of noninvasively monitoring the sites of development of lung metastatic lesions and their GCV-induced regression were assessed by SPECT with (131)I-FIAU. RESULTS: The results of this study showed that the lung metastases model of NG4TL4-TK cells could be successfully detected as early as 24 h after intravenous injection of tumor cells radiolabeled with (131)I-FIAU and also subsequently detected by extended monitoring with the intravenous injection of (131)I-FIAU on day 10. In mice treated with GCV, gamma-camera imaging demonstrated a significant growth inhibition of NG4TL4-TK cells of primary tumors and lung metastases on day 7 after initiating treatment. CONCLUSION: We conclude that this in vivo imaging approach will be useful for future studies of the lung metastases model and for the assessment of novel anticancer and antimetastatic therapies.

Brain SPECT imaging and whole-body biodistribution with [(123)I]ADAM - a serotonin transporter radiotracer in healthy human subjects.

INTRODUCTION: [(123)I]-2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ([(123)I]ADAM), a novel radiotracer, has promising application in the imaging of the serotonin transporter (SERT) in the human brain. In this study, the optimal scanning time for acquiring brain single photon emission computed tomography (SPECT) images was determined by performing dynamic SPECT studies at intervals from 0 to 6 h postinjection of [(123)I]ADAM. Additionally, radiation-absorbed doses were determined for three healthy human subjects using attenuation-corrected images. METHODS: Twelve subjects were randomized into one of three study groups as follows: whole-body distribution imaging (n=3), dynamic SPECT imaging (n=3) and brain SPECT imaging (n=6). The radiation-absorbed dose was calculated using MIRDOSE 3.0 software with attenuation-corrected data. The specific binding (SB) ratio of the brain stem was measured from dynamic SPECT images to determine the optimal scanning time. RESULTS: Dynamic SPECT images showed that the SB of the brain stem gradually increased to a maximum 4 h postinjection. Single photon emission computed tomography images at 4 h postinjection showed a high uptake of the radiotracer (SB) in the hypothalamus (1.40+/-0.12), brain stem (1.44+/-0.16), pons (1.13+/-0.14) and medial temporal lobe (0.59+/-0.10). The mean adult male value of effective dose was 3.37 x 10(-2) mSv/MBq with a 4.8-h urine-voiding interval. Initial high uptake in SERT-rich sites was demonstrated in the lung and brain. A prominent washout of the radiotracer from the lung further increased brain radioactivity that reached a peak value of 5.03% of injected dose 40 min postinjection. CONCLUSIONS: [(123)I]ADAM is a promising radiotracer for SPECT imaging of SERT in humans with acceptable dosimetry and high uptake in SERT-rich regions. Brain SPECT images taken within 4 h following injection show optimal levels of radiotracer uptake in known SERT sites. However, dynamic changes in lung SERT distribution must be carefully evaluated.

Longitudinal evaluation of tumor metastasis by an FDG-microPet/microCT dual-imaging modality in a lung carcinoma-bearing mouse model.

BACKGROUND: Histological methods are used to define the growth and response to various treatments of lung carcinoma in mice. The aim of the study was to evaluate a quantitative and 3D-tomographic microPET/microCT dual-image modality using 18F-fluorodeoxyglucose (FDG) to monitor the tumor progression in an experimental metastasis mouse model. MATERIALS AND METHODS: Six normal mice were subjected to FDG-microPET/microCT image scan to present the normal thorax morphology. Twenty-one 8-week-old male C57BL/6 mice were inoculated with 1 x 10(6) Lewis lung carcinoma cells (LLC1) through the lateral tail vein. FDG-microPET/microCT scans were performed on days 0, 5, 9, 13 and 18 (n=6) to monitor the growth of the tumor. MicroPET and microCT images were further used to monitor the metastasis of the lung carcinoma to the liver. Fifteen mice were sacrificed for biodistribution on days 0, 5, 9, 13 and 18 after the inoculation of lung carcinoma cells. RESULTS: The FDG-microPET/microCT dual-image modality showed that the growth of the tumor could be monitored longitudinally. The standard uptake value (SUV) of FDG increased from 0.63 +/- 0.05 on day 0 to 1.03 +/- 0.15 on day 18, reflecting the growth of the tumor in mice. The tumors located in the lung and liver could be clearly visualized by the fusion of microPET and microCT images, and further confirmed by whole-body autoradiography or H&E stain. CONCLUSION: By FDG-microPET, the increase in SUV provided an alternative for assessing the growth of a tumor in vivo. Our results suggest that the growth progression of lung carcinoma can be identified using the FDG-microPET/microCT dual-image modality longitudinally in mice.

Detection-ability evaluation of the PEImager for positron emission mammography applications.

This work is a pilot study of using a dual-head scanner in positron emission mammograph (PEM). A positron emission imager (PEImager) developed at our laboratory was used as a PEM prototype to obtain data. Dual-head projection imaging mode was used in the PEM study. An iterative algebraic reconstruction was employed to reconstruct projection data to obtain tomograms. A cylindrizal phantom filled with water was applied to simulate a breast and five hollow spheres (2 mm-10 mm diameters) filled with F-18 fluoride simulated tumors in the breast phantom. Preliminary data revealed that the locations and sizes of the hot spots in the breast phantom were determined from the reconstructed images. The ability to detect the tumor embedded in the radioactive water was evaluated. At a tumor-to-normal tissue ratio 20:1, a 3 mm tumor was detected; 5 mm and 10 mm tumors could be detected at the ratios of 10:1 and 5:1, respectively.

A three-dimensional registration method for automated fusion of micro PET-CT-SPECT whole-body images.

Micro positron emission tomography (PET) and micro single-photon emission computed tomography (SPECT), used for imaging small animals, have become essential tools in developing new pharmaceuticals and can be used, among other things, to test new therapeutic approaches in animal models of human disease, as well as to image gene expression. These imaging techniques can be used noninvasively in both detection and quantification. However, functional images provide little information on the structure of tissues and organs, which makes the localization of lesions difficult. Image fusion techniques can be exploited to map the functional images to structural images, such as X-ray computed tomography (CT), to support target identification and to facilitate the interpretation of PET or SPECT studies. Furthermore, the mapping of two functional images of SPECT and PET on a structural CT image can be beneficial for those in vivo studies that require two biological processes to be monitored simultaneously. This paper proposes an automated method for registering PET, CT, and SPECT images for small animals. A calibration phantom and a holder were used to determine the relationship among three-dimensional fields of view of various modalities. The holder was arranged in fixed positions on the couches of the scanners, and the spatial transformation matrix between the modalities was held unchanged. As long as objects were scanned together with the holder, the predetermined matrix could register the acquired tomograms from different modalities, independently of the imaged objects. In this work, the PET scan was performed by Concorde's microPET R4 scanner, and the SPECT and CT data were obtained using the Gamma Medica's X-SPECT/CT system. Fusion studies on phantoms and animals have been successfully performed using this method. For microPET-CT fusion, the maximum registration errors were 0.21 mm +/- 0.14 mm, 0.26 mm +/- 0.14 mm, and 0.45 mm +/- 0.34 mm in the X (right-left), Y (upper lower), and Z (rostral-caudal) directions, respectively; for the microPET-SPECT fusion, they were 0.24 mm +/- 0.14 mm, 0.28 mm +/- 0.15 mm, and 0.54 mm +/- 0.35 mm in the X, Y, and Z directions, respectively. The results indicate that this simple method can be used in routine fusion studies.