Diagnostic Accuracy of MR Spectroscopic Imaging and 18F-FET PET for Identifying Glioma: A Biopsy-Controlled Hybrid PET/MRI Study.

Contrast-enhanced MRI is the method of choice for brain tumor diagnostics, despite its low specificity for tumor tissue. This study compared the contribution of MR spectroscopic imaging (MRSI) and amino acid PET to improve the detection of tumor tissue. Methods: In 30 untreated patients with suspected glioma, O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) PET; 3-T MRSI with a short echo time; and fluid-attenuated inversion recovery, T2-weighted, and contrast-enhanced T1-weighted MRI were performed for stereotactic biopsy planning. Serial samples were taken along the needle trajectory, and their masks were projected to the preoperative imaging data. Each sample was individually evaluated neuropathologically. 18F-FET uptake and the MRSI signals choline (Cho), N-acetyl-aspartate (NAA), creatine, myoinositol, and derived ratios were evaluated for each sample and classified using logistic regression. The diagnostic accuracy was evaluated by receiver operating characteristic analysis. Results: On the basis of the neuropathologic evaluation of tissue from 88 stereotactic biopsies, supplemented with 18F-FET PET and MRSI metrics from 20 areas on the healthy-appearing contralateral hemisphere to balance the glioma/nonglioma groups, 18F-FET PET identified glioma with the highest accuracy (area under the receiver operating characteristic curve, 0.89; 95% CI, 0.81-0.93; threshold, 1.4 × background uptake). Among the MR spectroscopic metabolites, Cho/NAA normalized to normal brain tissue showed the highest diagnostic accuracy (area under the receiver operating characteristic curve, 0.81; 95% CI, 0.71-0.88; threshold, 2.2). The combination of 18F-FET PET and normalized Cho/NAA did not improve the diagnostic performance. Conclusion: MRI-based delineation of gliomas should preferably be supplemented by 18F-FET PET.

18F-FET-PET-guided gross total resection improves overall survival in patients with WHO grade III/IV glioma: moving towards a multimodal imaging-guided resection.

PURPOSE: PET using radiolabeled amino acid [18F]-fluoro-ethyl-L-tyrosine (FET-PET) is a well-established imaging modality for glioma diagnostics. The biological tumor volume (BTV) as depicted by FET-PET often differs in volume and location from tumor volume of contrast enhancement (CE) in MRI. Our aim was to investigate whether a gross total resection of BTVs defined as < 1 cm3 of residual BTV (PET GTR) correlates with better oncological outcome. METHODS: We retrospectively analyzed imaging and survival data from patients with primary and recurrent WHO grade III or IV gliomas who underwent FET-PET before surgical resection. Tumor overlap between FET-PET and CE was evaluated. Completeness of FET-PET resection (PET GTR) was calculated after superimposition and semi-automated segmentation of pre-operative FET-PET and postoperative MRI imaging. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. RESULTS: From 30 included patients, PET GTR was achieved in 20 patients. Patients with PET GTR showed improved median OS with 19.3 compared to 13.7 months for patients with residual FET uptake (p = 0.007; HR 0.3; 95% CI 0.12-0.76). This finding remained as independent prognostic factor after performing multivariate analysis (HR 0.19, 95% CI 0.06-0.62, p = 0.006). Other survival influencing factors such as age, IDH-mutation, MGMT promotor status, and adjuvant treatment modalities were equally distributed between both groups. CONCLUSION: Our results suggest that PET GTR improves the OS in patients with WHO grade III or IV gliomas. A multimodal imaging approach including FET-PET for surgical planning in newly diagnosed and recurrent tumors may improve the oncological outcome in glioma patients.

Effects of Combined Vitamin K2 and Vitamin D3 Supplementation on Na[18F]F PET/MRI in Patients with Carotid Artery Disease: The INTRICATE Rationale and Trial Design.

INTRICATE is a prospective double-blind placebo-controlled feasibility study, assessing the influence of combined vitamin K2 and vitamin D3 supplementation on micro-calcification in carotid artery disease as imaged by hybrid Sodium [18F]Fluoride (Na[18F]F) positron emission tomography (PET)/ magnetic resonance imaging (MRI). Arterial calcification is an actively regulated process and results from the imbalance between calcification promoting and inhibiting factors. Considering the recent advancements in medical imaging, ultrasound (US), PET/MRI, and computed tomography (CT) can be used for the selection and stratification of patients with atherosclerosis. Fifty-two subjects with asymptomatic carotid artery disease on at least one side of the neck will be included in the study. At baseline, an Na[18F]F PET/MRI and CT examination will be performed. Afterwards, subjects will be randomized (1:1) to a vitamin K (400 µg MK-7/day) and vitamin D3 (80 µg/day) or to placebo. At the 3-month follow-up, subjects will undergo a second Na[18F]F PET/MRI and CT scan. The primary endpoint is the change in Na[18F]F PET/MRI (baseline vs. after 3 months) in the treatment group as compared to the placebo arm. Secondary endpoints are changes in plaque composition and in blood-biomarkers. The INTRICATE trial bears the potential to open novel avenues for future large scale randomized controlled trials to intervene in the plaque development and micro-calcification progression.

Sodium [18F]Fluoride PET Can Efficiently Monitor In Vivo Atherosclerotic Plaque Calcification Progression and Treatment.

Given the high sensitivity and specificity of sodium [18F]Fluoride (Na[18F]F) for vascular calcifications and positive emerging data of vitamin K on vascular health, the aim of this study is to assess the ability of Na[18F]F to monitor therapy and disease progression in a unitary atherosclerotic mouse model. ApoE-/- mice were placed on a Western-type diet for 12-weeks and then split into four groups. The early stage atherosclerosis group received a chow diet for an additional 12-weeks, while the advanced atherosclerosis group continued the Western-type diet. The Menaquinone-7 (MK-7) and Warfarin groups received MK-7 or Warfarin supplementation during the additional 12-weeks, respectively. Control wild type mice were fed a chow diet for 24-weeks. All of the mice were scanned with Na[18F]F using a small animal positron emission tomography (PET)/computed tomography (CT). The Warfarin group presented spotty calcifications on the CT in the proximal aorta. All of the spots corresponded to dense mineralisations on the von Kossa staining. After the control, the MK-7 group had the lowest Na[18F]F uptake. The advanced and Warfarin groups presented the highest uptake in the aortic arch and left ventricle. The advanced stage group did not develop spotty calcifications, however Na[18F]F uptake was still observed, suggesting the presence of micro-calcifications. In a newly applied mouse model, developing spotty calcifications on CT exclusively in the proximal aorta, Na[18F]F seems to efficiently monitor plaque progression and the beneficial effects of vitamin K on cardiovascular disease.

Locking and loading the bullet against micro-calcification.

AIMS: Despite recent medical advances, cardiovascular disease remains the leading cause of death worldwide. As (micro)-calcification is a hallmark of atherosclerosis, this review will elaborately discuss advantages of sodium fluoride positron emission tomography (PET) as a reliable cardiovascular imaging technique for identifying the early onset of vascular calcification (i.e. locking onto the target). We assess state-of-the-art meta-analysis and clinical studies of possible treatment options and evaluate the concept of vitamin K supplementation to preserve vascular health (i.e. loading the bullet). METHODS AND RESULTS: After a structured PubMed search, we identified 18F-sodium fluoride (18F-NaF) PET as the most suitable technique for detecting micro-calcification. Presenting the pros and cons of available treatments, vitamin K supplementation should be considered as a possible safe and cost-effective option to inhibit vascular (micro)-calcification. CONCLUSION: This review demonstrates need for more extensive research in the concept of vitamin K supplementation (i.e. loading the bullet) and recommends monitoring the effects on vascular calcification using 18F-NaF PET (i.e. locking onto the target).

Contemporary considerations in adjuvant radioiodine treatment of adults with differentiated thyroid cancer.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy with a growing incidence worldwide. The initial conventional management is surgery, followed by consideration of 131 I treatment that includes three options. These are termed remnant ablation (targeting benign thyroid remnant), adjuvant (targeting presumed microscopic DTC) and known disease (targeting macroscopic DTC) treatments. Some experts mostly rely on clinicopathologic assessment for recurrence risk to select patients for the 131 I treatment. Others, in addition, apply radioiodine imaging to guide their treatment planning, termed theranostics (aka theragnostics or radiotheragnostics). In patients with low-risk DTC, remnant ablation rather than adjuvant treatment is generally recommended and, in this setting, the ATA recommends a low 131 I activity. 131 I adjuvant treatment is universally recommended in patients with high-risk DTC (a primary tumor of any size with gross extrathyroidal extension) and is generally recommended in intermediate-risk DTC (primary tumor >4 cm in diameter, locoregional metastases, microscopic extrathyroidal extension, aggressive histology or vascular invasion). The optimal amount of 131 I activity for adjuvant treatment is controversial, but experts reached a consensus that the 131 I activity should be greater than that for remnant ablation. The main obstacles to establishing timely evidence through randomized clinical trials for 131 I therapy include years-to-decades delay in recurrence and low disease-specific mortality. This mini-review is intended to update oncologists on the most recent clinical, pathologic, laboratory and imaging variables, as well as on the current 131 I therapy-related definitions and management paradigms, which should optimally equip them for individualized patient guidance and treatment.

Targeting of prostate-specific membrane antigen for radio-ligand therapy of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer has extremely high risk of relapse due to the lack of targeted therapies, intra- and inter-tumoral heterogeneity, and the inherent and acquired resistance to therapies. In this study, we evaluate the potential of prostate-specific membrane antigen (PSMA) as target for radio-ligand therapy (RLT). METHODS: Tube formation was investigated after incubation of endothelial HUVEC cells in tumor-conditioned media and monitored after staining using microscopy. A binding study with 68Ga-labeled PSMA-addressing ligand was used to indicate targeting potential of PSMA on tumor-conditioned HUVEC cells. For mimicking of the therapeutic application, tube formation potential and vitality of tumor-conditioned HUVEC cells were assessed following an incubation with radiolabeled PSMA-addressing ligand [177Lu]-PSMA-617. For in vivo experiments, NUDE mice were xenografted with triple-negative breast cancer cells MDA-MB231 or estrogen receptor expressing breast cancer cells MCF-7. Biodistribution and binding behavior of [68Ga]-PSMA-11 was investigated in both tumor models at 30 min post injection using µPET. PSMA- and CD31-specific staining was conducted to visualize PSMA expression and neovascularization in tumor tissue ex vivo. RESULTS: The triple-negative breast cancer cells MDA-MB231 showed a high pro-angiogenetic potential on tube formation of endothelial HUVEC cells. The induced endothelial expression of PSMA was efficiently addressed by radiolabeled PSMA-specific ligands. 177Lu-labeled PSMA-617 strongly impaired the vitality and angiogenic potential of HUVEC cells. In vivo, as visualized by µPET, radiolabeled PSMA-ligand accumulated specifically in the triple-negative breast cancer xenograft MDA-MB231 (T/B ratio of 43.3 ± 0.9), while no [68Ga]-PSMA-11 was detected in the estrogen-sensitive MCF-7 xenograft (T/B ratio of 1.1 ± 0.1). An ex vivo immunofluorescence analysis confirmed the localization of PSMA on MDA-MB231 xenograft-associated endothelial cells and also on TNBC cells. CONCLUSIONS: Here we demonstrate PSMA as promising target for two-compartment endogenous radio-ligand therapy of triple-negative breast cancer.

Relevant tumor sink effect in prostate cancer patients receiving 177Lu-PSMA-617 radioligand therapy.

AIM: In metastatic prostate cancer patients PSMA targeting radioligands have gained significant impact as theranostic probes. In this study a correlation between total tumor volume (TTV) and measured kidney dose as well as salivary glands (SG) uptake in 177Lu-PSMA-617 therapy was evaluated. METHODS: Eleven consecutive prostate cancer patients receiving a first cylcle of 177Lu-PSMA-617 (administered activity of approximately 6GBq) were included. The 68Ga-PSMA-11 PET/CT scan previous to therapy was used to determine TTV and SG uptake (glandulae submandibularis) employing PMOD version 3.403 with different 68Ga-PSMA-11 thresholds based on the standardized uptake value (SUV).The kidney dose was estimated with the software ULMDOS using planar whole-body scintigrams. RESULTS: Kidney dose and SG uptake was inversely correlated to TTV, indicating high kidney dose and high SG uptake in case of low tumor load and low kidney dose and low SG uptake in case of high tumor load. CONCLUSION: Our data support the hypothesis that in 177Lu-PSMA-617 therapy an individualized treatment activity based on total tumor volume could be beneficiary.

PSA levels, PSA doubling time, Gleason score and prior therapy cannot predict measured uptake of [68Ga]PSMA-HBED-CC lesion uptake in recurrent/metastatic prostate cancer.

AIM: To assess whether clinical prostate cancer (PCA) related factors and therapy status can predict the degree of tracer uptake on [68Ga]PSMA-HBED-CC PET/CT. MATERIALS & METHODS: We retrospectively studied 124 patients with recurrent an/or metastatic PCA who underwent [68Ga]PSMAHBED-CC PET/CT. The maximum standardized uptake value (SUVmax) was determined in the prostate bed as well as in three size categories (≤ 5 mm, > 5-15 mm, > 15 mm) in pelvic lymph node, extrapelvic lymph node, bone and visceral metastases. RESULTS: Significant positive correlations between lesion size and SUVmax were found in pelvic lymph node metastases > 5 -≤15 mm (Spearmans rho = 0.502, p = 0.002) as well as in extrapelvic lymph node metastases5 mm (rho = 0.314, p = 0.033) and > 5 ≤-15 mm (rho = 0.614, p < 0.001). SUVmax tended to be higher in the largest diameter category in each anatomic station than in the middle and lower categories. We were unable to find evidence for a relationship between SUVmax and PSA, PSAdt, Gleason score, androgen deprivation therapy, radiation therapy or chemotherapy status. CONCLUSION: Measured tracer uptake in [68Ga]PSMA-HBED-CC PET/CT in patients with recurrent/metastasized prostate cancer is significantly influenced by lesion size as a result of partial volume effects in the very small lesions. Clinical indicators of aggressive prostate cancer behaviour such as PSA levels, PSA doubling time or the Gleason score of the primary tumour, as well as the androgen deprivation therapy, radiation therapy or chemotherapy status are not related to measured tracer uptake. ZIEL:: Beantwortung der Frage ob klinisch bestimmbare Faktoren und Therapiestatus bei Prostatakarzinom (PCA) eine Vorhersage zur Traceranreicherung in [68Ga]PSMA-HBED-CC PET/CT liefern können.Material & Methoden: 124 Patienten mit rezidiviertem und/oder metastasiertem PCA die [68Ga]PSMA-HBED-CC PET/CT untergingen, wurden retrospektiv untersucht. Der maximum Standardized Uptake Value (SUVmax) wurde in der Prostataloge gemessen sowie in drei Größen-Kategorien ( 5 mm, > 5-15 mm, > 15 mm) in Metastasen in den pelvinen Lymphknoten-, extrapelvinen Lymphknoten-, Knochen- und viszeralen Metastasen. ERGEBNISSE: Signifikant positive Korrelationen zwischen Läsionsgröße und SUVmax wurden in pelvinen Lymphknotenmetastasen > 5 -≤15 mm (Spearmans rho = 0.502, p = 0.002), extrapelvinen Lymphknotenmetastasen5 mm (rho = 0.314, p = 0.033) und > 5 -≤15 mm (rho = 0.614, p < 0.001) gefunden. Für jede anatomische Lokalisation wurde ein höherer Wert SUVmax innerhalb der größten Kategorie verglichen zu mittleren und kleinsten Kategorie gefunden.

Synthesis, Radiosynthesis, and Preliminary in vitro and in vivo Evaluation of the Fluorinated Ceramide Trafficking Inhibitor (HPA-12) for Brain Applications.

Ceramide levels are increased in blood and brain tissue of Alzheimer's disease (AD) patients. Since the ceramide transporter protein (CERT) is the only known protein able to mediate non-vesicular transfer of ceramide between organelle membranes, the modulation of CERT function may impact on ceramide accumulation. The competitive CERT inhibitor N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide (HPA-12) interferes with ceramide trafficking. To understand the role of ceramide/CERT in AD, HPA-12 can be a useful tool to modulate ceramide trafficking. Here we first report the synthesis and in vitro properties of HPA-12 radiolabeled with fluorine-18 and present preliminary in vitro and in vivo positron emission tomography (PET) imaging and biodistribution data. In vitro results demonstrated that the fluorination did not alter the biological properties of HPA-12 since the [fluorine-19]HPA-12, interferes with 5-DMB-ceramide trafficking in HeLa cells. Radiolabeled HPA-12, [fluorine-18]HPA-12, was obtained with a radiochemical yield of 90% and a specific activity of 73 MBq/µmol. PET imaging on wild-type mice showed hepatobiliary clearance and a brain uptake on the order of 0.3 standard uptake value (SUV) one hour post injection. Furthermore, the biodistribution data showed that after removal of the blood by intracardial perfusion, radioactivity was still measurable in the brain demonstrating that the [fluorine-18]HPA-12 crosses the blood brain barrier and is retained in the brain.

Individualized dosimetry-based activity reduction of 9°Y-DOTATOC prevents severe and rapid kidney function deterioration from peptide receptor radionuclide therapy.

PURPOSE: Assessment of kidney function evolution after (90)Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney. METHODS: In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq (111)In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose-toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using (51)Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL). RESULTS: Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33% was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT. CONCLUSION: Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for (90)Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity.

Do androgens control the uptake of 18F-FDG, 11C-choline and 11C-acetate in human prostate cancer cell lines?

PURPOSE: The aim of this study was to evaluate the impact of androgen ablation therapy in different prostate cancer (PCa) cell lines--reflecting different stages of the disease--on (18)F-fluorodeoxyglucose (FDG), 11C-choline and 11C-acetate uptake. METHODS: Uptake experiments were performed in androgen-sensitive (LNCaP, PC346C) and independent cell lines (22Rv1, PC346DCC, PC-3) as well as in a benign prostatic hyperplasia (BPH-1) cell line. Tracer uptake was assessed under androgen ablation. Results of the cancer cell lines were normalized to those of BPH-1. To evaluate the effect of androgen on the uptake of 18F-FDG, 11C-choline and 11C-acetate in PCa cell lines, 10(-8) M R1881, 10(-10) M R1881, the combination of 10(-10) M R1881 plus 10(-6) M Casodex or 10(-6) M Casodex alone were added in parallel cell cultures 1 day before uptake experiments. Uptake in androgen-supplemented cell cultures was compared to the uptake under androgen deprivation. Uptake was corrected for cell number using protein content. RESULTS: Compared to BPH-1, a higher 18F-FDG uptake was observed only in PC346C cells, whereas a higher 11C-choline and markedly increased 11C-acetate uptake was seen in all cancer cell lines. Androgens significantly modulated the uptake of 18F-FDG in LNCaP, PC346C and 22Rv1 cells, and of 11C-choline in the PC346C and 22Rv1 cell line. No androgenic effect on 11C-choline and 18F-FDG uptake was observed in PC-3 and PC346DCC cells. 11C-Acetate uptake was independent of androgen status in all PCa cell lines studied. CONCLUSION: 18F-FDG uptake in PCa cell lines showed the highest variability and strongest androgen effect, suggesting its poor potential for metabolic imaging of advanced PCa. In contrast to 18F-FDG and 11C-choline, 11C-acetate uptake was unaffected by androgens and thus 11C-acetate seems best for monitoring PCa progression.

Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)-From insights into human memory to therapy of its dysfunction.

Noninvasive stimulation of the brain by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) has driven important discoveries in the field of human memory functions. Stand-alone or in combination with other brain mapping techniques noninvasive brain stimulation can assess issues such as location and timing of brain activity, connectivity and plasticity of neural circuits and functional relevance of a circumscribed brain area to a given cognitive task. In this emerging field, major advances in technology have been made in a relatively short period. New stimulation protocols and, especially, the progress in the application of tDCS have made it possible to obtain longer and much clearer inhibitory or facilitatory effects even after the stimulation has ceased. In this introductory review, we outline the basic principles, discuss technical limitations and describe how noninvasive brain stimulation can be used to study human memory functions in vivo. Though improvement of cognitive functions through noninvasive brain stimulation is promising, it still remains an exciting challenge to extend the use of TMS and tDCS from research tools in neuroscience to the treatment of neurological and psychiatric patients.

Lexical decision of nonwords and pseudowords in humans: a positron emission tomography study.

In this functional positron emission tomography study brain activations during an auditory lexical decision task with two experimental conditions were investigated. First, the subjects had to discriminate between real words and nonwords; second, real words varied with pseudowords. Comparing each of these tasks to an auditory control condition we found bilateral activation of the superior temporal and inferior frontal gyrus, lateralized to the left in the pseudoword condition. The comparison of the lexical decision tasks revealed higher rCBF during the pseudo-/real word decisions within BA 47, adjacent to Broca's area, and the anterior cingulate. The data support the notion that the lexical decision during a nonword task is mainly based on a phonological discrimination process, whereas a pseudoword task more strongly requires lexical access resulting in activation of BA 47.

Correlation of cerebral blood flow and treatment effects of repetitive transcranial magnetic stimulation in depressed patients.

The aims of this study were to: (1) assess the effects of repetitive transcranial magnetic stimulation (rTMS) on brain activity in depressed patients as measured by single photon emission tomography (SPECT); (2) evaluate the predictive value of brain SPECT on the antidepressant efficacy of rTMS. Patients (n=17) received 1600 rTMS stimuli at a rate of 10 Hz, 5 days per week for 2 weeks to the left dorsolateral prefrontal cortex. Whole brain SPECT data were acquired using Tc99m-Bicisate. Regional cerebral blood flow (rCBF) was correlated with the % change in the 28-item Hamilton Depression Rating Scale Score (Delta-HDRS) and a semiquantitative region of interest (ROI) analysis was conducted. Prior to rTMS there was a significant left-right asymmetry favoring the right, whereas 2 weeks after the rTMS treatment this asymmetry was reversed. The rCBF in limbic structures was negatively correlated with the outcome and rCBF in several neocortical areas was positively correlated. Brain SPECT can provide information about mechanisms of action of rTMS and may have predictive value for the antidepressant efficacy of rTMS.

Functional magnetic resonance imaging detects activation of the visual association cortex during laser acupuncture of the foot in humans.

The aim of this study was to investigate the effect of laser acupuncture on cerebral activation. Using functional magnetic imaging (fMRI) cortical activations during laser acupuncture at the left foot (Bladder 67) and dummy acupuncture, were compared employing a block design in ten healthy male volunteers. All experiments were done on a 1.5 Tesla magnetic resonance scanner equipped with a circular polarized head coil. During laser acupuncture, we found activation in the cuneus corresponding to Brodmann Area (BA) 18 and the medial occipital gyrus (BA 19) of the ipsilateral visual cortex. Placebo stimulation did not show any activation. We could demonstrate that laser acupuncture of a specific acupoint, empirically related to ophthalmic disorders, leads to activation of visual brain areas, whereas placebo acupuncture does not. These results indicate that fMRI has the potential to elucidate effects of acupuncture on brain activity.

Visual cortex excitability increases during visual mental imagery--a TMS study in healthy human subjects.

Previous neuroimaging studies provided evidence that visual mental imagery relies, in part, on the primary visual cortex. We hypothesized that, analogous to the finding that motor imagery increases the excitability of motor cortex, visual imagery should increase visual cortex excitability, as indexed by a decrease in the phosphene threshold (PT). In order to test visual cortex excitability, the primary visual cortex was stimulated with transcranial magnetic stimulation (TMS), so as to elicit phosphenes in the right lower visual quadrant. Subjects performed a visual imagery task and an auditory control task. We applied TMS with increasing intensity to determine the PT for each subject. Independent of the quadrant in which subjects placed their visual images, imagery decreased PT compared to baseline PT; in contrast, the auditory task did not change PT. These findings demonstrate for the first time a short-term, task-dependent modulation of PT. These results constitute evidence that early visual areas participate in visual imagery processing.