Prognostic impact of myocardial perfusion single photon emission computed tomography in patients with major extracardiac findings by computed tomography for attenuation correction.

BACKGROUND: Attenuation correction computed tomography (CT) contributes to an improvement in the diagnostic accuracy of myocardial perfusion imaging (MPI) by single photon emission tomography (SPECT). The aim of this study was to explore the prognosis of patients with major findings by CT according to the results of MPI. METHODS AND RESULTS: 1506 patients who underwent MPI by SPECT were retrospectively included. Attenuation correction CT images were systematically analyzed for major and minor abnormalities. 830 (55.1%) and 212 (14.1%) patients had minor and major extracardiac findings, respectively. Among patients with major extracardiac findings, the abnormality was previously unknown in 113 (53.3%) patients. 90 (41.9%) had abnormal MPI, 73 (34.4%) had a myocardial infarction scar, 55 (25.9%) had myocardial ischemia, and 38 (17.7%) patients had both myocardial infarction scar and myocardial ischemia. Among the 201 patients available for survival analysis, there were 67 (31.2%) deaths over a follow-up period of 3.2±1.3 years. There was no significant impact on survival arising from MPI, whatever the result. The results were the same among the 103 patients with previously unknown major extracardiac findings. CONCLUSION: Extracardiac findings by CT during MPI are frequent. Patients with major extracardiac findings have a poor mid-term outcome, whatever the results of the myocardial perfusion imaging. Extracardiac findings should be systematically checked when attenuation correction CT is performed.

Feasibility and accuracy of gated blood pool SPECT equilibrium radionuclide ventriculography for the assessment of left and right ventricular volumes and function in patients with left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) require serial assessment of right and left ventricular (RV & LV) volumes and function. Because the RV is not assisted, its function is a critical determinant of the hemodynamic and contributes significantly to postoperative morbidity and mortality. We evaluated the feasibility and the accuracy of tomographic-equilibrium radionuclide ventriculography (t-ERV) for the assessment of patients with LVADs. METHODS: Twenty-four patients with LVAD underwent t-ERV. Because of the limited acoustic window, transthoracic echocardiography (TTE) was only feasible in 19 patients. Functional evaluation including six-minute walk test (6MWT) and peak oxygen consumption (POC) was performed in 18 patients. Nine patients underwent a cardiac multidetector computed tomography (MDCT). Eight patients underwent a second evaluation by ERV 4.3 ± 1.4 months later. RESULTS: Reliability between t-ERV and MDCT for LV end-diastolic volume, LV end-systolic volume, LV ejection fraction, RV end-diastolic volume, RV end-systolic volume, and RV ejection fraction (RVEF) was 0.900 (P = .001), 0.911 (P = .001), 0.765 (P = .021), 0.728 (P = .042), 0.875 (P = .004), and 0.781 (P = .023), respectively. There was no correlation between t-ERV and RV systolic parameters assessed by TTE. RVEF was correlated with POC (R = 0.521; P = .027). A cut-off value of 40% for RVEF measured by t-ERV could discriminate patients with poor functional status (P = .048 for NYHA stage; P = .016 for 6MWT and P = .007 for POC). CONCLUSION: t-ERV is a simple, reproducible, and an accurate technique for the assessment of RV function in patients with LVADs and warrants consideration in the evaluation and monitoring of symptomatic patients.

Reduced Regional Cerebral Blood Flow Measured by 99mTc-Hexamethyl Propylene Amine Oxime Single-Photon Emission Computed Tomography in Microgravity Simulated by 5-Day Dry Immersion.

Microgravity induces a cephalad fluid shift that is responsible for cephalic venous stasis that may increase intracranial pressure (ICP) in astronauts. However, the effects of microgravity on regional cerebral blood flow (rCBF) are not known. We therefore investigated changes in rCBF in a 5-day dry immersion (DI) model. Moreover, we tested thigh cuffs as a countermeasure to prevent potential microgravity-induced modifications in rCBF. Around 18 healthy male participants underwent 5-day DI with or without a thigh cuffs countermeasure. They were randomly allocated to a control (n=9) or cuffs (n=9) group. rCBF was measured 4days before DI and at the end of the fifth day of DI (DI5), using single-photon emission computed tomography (SPECT) with radiopharmaceutical 99mTc-hexamethyl propylene amine oxime (99mTc-HMPAO). SPECT images were processed using statistical parametric mapping (SPM12) software. At DI5, we observed a significant decrease in rCBF in 32 cortical and subcortical regions, with greater hypoperfusion in basal ganglia (right putamen peak level: z=4.71, p uncorr<0.001), bilateral occipital regions (left superior occipital peak level: z=4.51, p uncorr<0.001), bilateral insula (right insula peak level: 4.10, p uncorr<0.001), and bilateral inferior temporal (right inferior temporal peak level: 4.07, p uncorr<0.001). No significant difference was found between the control and cuffs groups on change in rCBF after 5days of DI. After a 5-day DI, we found a decrease in rCBF in cortical and subcortical regions. However, thigh cuffs countermeasure failed to prevent hypoperfusion. To date, this is the first study measuring rCBF in DI. Further investigations are needed in order to better understand the underlying mechanisms in cerebral blood flow (CBF) changes after exposure to microgravity.

Comparison of commercial dosimetric software platforms in patients treated with 177 Lu-DOTATATE for peptide receptor radionuclide therapy.

PURPOSE: The aim of this study was to quantitatively compare five commercial dosimetric software platforms based on the analysis of clinical datasets of patients who benefited from peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE (LUTATHERA® ). METHODS: The dosimetric analysis was performed on two patients during two cycles of PRRT with 177 Lu. Single photon emission computed tomography/computed tomography images were acquired at 4, 24, 72, and 192 h post injection. Reconstructed images were generated using Dosimetry Toolkit® (DTK) from Xeleris™ and HybridRecon-Oncology version_1.3_Dicom (HROD) from HERMES. Reconstructed images using DTK were analyzed using the same software to calculate time-integrated activity coefficients (TIAC), and mean absorbed doses were estimated using OLINDA/EXM V1.0 with mass correction. Reconstructed images from HROD were uploaded into PLANET® OncoDose from DOSIsoft, STRATOS from Phillips, Hybrid Dosimetry Module™ from HERMES, and SurePlan™ MRT from MIM. Organ masses, TIACs, and mean absorbed doses were calculated from each application using their recommendations. RESULTS: The majority of organ mass estimates varied by <9.5% between all platforms. The highest variability for TIAC results between platforms was seen for the kidneys (28.2%) for the two patients and the two treatment cycles. Relative standard deviations in mean absorbed doses were slightly higher compared with those observed for TIAC, but remained of the same order of magnitude between all platforms. CONCLUSIONS: When applying a similar processing approach, results obtained were of the same order of magnitude regardless of the platforms used. However, the comparison of the performances of currently available platforms is still difficult as they do not all address the same parts of the dosimetric analysis workflow. In addition, the way in which data are handled in each part of the chain from data acquisition to absorbed doses may be different, which complicates the comparison exercise. Therefore, the dissemination of commercial solutions for absorbed dose calculation calls for the development of tools and standards allowing for the comparison of the performances between dosimetric software platforms.

Relevance of the skewness index in DTI exploration of multiple sclerosis.

OBJECT: To this day, no parameter can really monitor the progression of multiple sclerosis (MS). In this study, an index the skewness (S) derived from parameters calculated in diffusion tensor imaging (DTI) has been tested on MS patients for its ability to monitor the disease course. MATERIALS AND METHODS: Eighteen patients underwent two examinations within 3 months consisting of a clinical evaluation (EDSS) and DTI acquisitions on a 1.5 T imager. Tensor was calculated thanks to"home-made" software. Mean diffusivity (MD) and fractional anisotropy (FA) histograms were described for normal-appearing white matter (NAWM) and gray matter (GM) of patients with S and also with usually indices peak position (pp) and peak height (ph) for the whole group of patients and for two separate groups according to their clinical status (EDSS < or = 3 and EDSS > 3 at month 0). RESULTS: Although no significant clinical evolution is observed over 3 months, S in GM showed a significant shift for both MD/FA histograms towards abnormal values for the whole group of patients (p = 0.02/p = 0.04) and for the group with EDSS

Quantification of myocardial 99mTc-labeled bisphosphonate uptake with cadmium zinc telluride camera in patients with transthyretin-related cardiac amyloidosis.

PURPOSE: We aimed to compare different methods for semi-quantitative analysis of cardiac retention of bone tracers in patients with cardiac transthyretin amyloidosis (ATTR). METHODS: Data from 67 patients with ATTR who underwent both conventional whole-body scan and a CZT myocardial SPECT (DSPECT, Spectrum Dynamics) 3 h after injection of 99mTc-labeled bone tracer were analyzed. Visual scoring of cardiac retention was performed on whole-body scan according to Perugini 4-point grading system from 0 (no uptake) to 3 (strong cardiac uptake with mild/absent bone uptake). A planar heart-to-background (H:B) ratio was calculated using whole-body scan (wb-H:B). CZT SPECT was quantified using three methods: planar H:B ratio calculated from anterior reprojection (ant-H:B), left anterior oblique reprojection (LAO-H:B), and 3D-H:B ratio calculated from transaxial slices as mean counts in a VOI encompassing the heart divided by background VOI in the contralateral lung. Interventricular septal thickness was obtained using echocardiography. RESULTS: H:Bs obtained from planar and reprojected data were not statistically different (wb-H:B, 2.05 ± 0.64, ant-H:B, 1.97 ± 0.61, LAO-H:B, 2.06 ± 0.64, all p = ns). However, 3D-H:B was increased compared to planar H:Bs (3D-H:B, 4.06 ± 1.77, all p < 0.0001 vs. wb-H:B, ant-H:B, and LAO-H:B). Bland-Altman plots demonstrated that the difference between 3D and planar H:Bs increased with the mean value of myocardial uptake. 3D-H:B was best correlated to septal thickness (r = 0.45, p < 0.001). Finally, abnormal right ventricular uptake was associated with higher values of cardiac retention. CONCLUSION: 3D semi-quantitative analysis of CZT SPECT optimized the assessment of 99mTc-labeled bone tracer myocardial uptake in patients with cardiac amyloidosis.

Proton magnetic resonance spectroscopic imaging in newly diagnosed glioblastoma: predictive value for the site of postradiotherapy relapse in a prospective longitudinal study.

PURPOSE: To investigate the association between magnetic resonance spectroscopic imaging (MRSI)-defined, metabolically abnormal tumor regions and subsequent sites of relapse in data from patients treated with radiotherapy (RT) in a prospective clinical trial. METHODS AND MATERIALS: Twenty-three examinations were performed prospectively for 9 patients with newly diagnosed glioblastoma multiforme studied in a Phase I trial combining Tipifarnib and RT. The patients underwent magnetic resonance imaging (MRI) and MRSI before treatment and every 2 months until relapse. The MRSI data were categorized by the choline (Cho)/N-acetyl-aspartate (NAA) ratio (CNR) as a measure of spectroscopic abnormality. CNRs corresponding to T1 and T2 MRI for 1,207 voxels were evaluated before RT and at recurrence. RESULTS: Before treatment, areas of CNR2 (CNR > or =2) represented 25% of the contrast-enhancing (T1CE) regions and 10% of abnormal T2 regions outside T1CE (HyperT2). The presence of CNR2 was often an early indicator of the site of relapse after therapy. In fact, 75% of the voxels within the T1CE+CNR2 before therapy continued to exhibit CNR2 at relapse, compared with 22% of the voxels within the T1CE with normal CNR (p < 0.05). The location of new contrast enhancement with CNR2 corresponded in 80% of the initial HyperT2+CNR2 vs. 20.7% of the HyperT2 voxels with normal CNR (p < 0.05). CONCLUSION: Metabolically active regions represented a small percentage of pretreatment MRI abnormalities and were predictive for the site of post-RT relapse. The incorporation of MRSI data in the definition of RT target volumes for selective boosting may be a promising avenue leading to increased local control of glioblastomas.

Spleno-hepatic index to predict portal hypertension by equilibrium radionuclide ventriculography.

BACKGROUND: Structural and morphological changes accompanying liver cirrhosis lead to portal hypertension (PHT), which is the first step of most of the complications in patients with liver cirrhosis. Therefore, the development of noninvasive techniques to detect PHT is crucial for prognosis and treatment. AIM: The aim of our study was to assess the diagnostic performance of a new spleno-hepatic index (SHI) measured from equilibrium radionuclide ventriculography (ERV) images in detecting patients with cirrhotic PHT. METHODS AND RESULTS: A total of 38 patients with PHT were compared with 30 controls without liver disease. The SHI was measured on the sum of the tomographic images from the ERV and calculated according to the following formula: SHI=(mean splenic count×longest hepatic length)/mean hepatic count. Mean SHI was 54±14 and 36±8 (P<0.001) among patients with PHT and controls, respectively. A cutoff value of 40 for the SHI allowed a sensitivity of 90% and specificity of 77% to detect PHT. SHI greater than 51 was 100% specific. In a subset of 25 patients, SHI was not correlated with hepatic venous pressure gradient measured invasively in the right hepatic vein (R=-0.08, P=0.70). CONCLUSION: Quantification of SHI derived from ERV could be used to detect liver cirrhosis with PHT although it is not linearly correlated with the hepatic venous pressure gradient. SHI should be considered as a useful index for the identification of PHT in patients referred for the detection/exploration of cirrhotic cardiomyopathy by ERV.

Nonlinearity in MCF7 Cell Survival Following Exposure to Modulated 6 MV Radiation Fields: Focus on the Dose Gradient Zone.

The study of cell survival following exposure to nonuniform radiation fields is taking on particular interest because of the increasing evidence of a nonlinear relationship at low doses. We conducted in vitro experiments using the MCF7 breast cancer cell line. A 2.4 × 2.4 cm(2) square area of a T25 flask was irradiated by a Varian Novalis accelerator delivering 6 MV photons. Cell survival inside the irradiation field, in the dose gradient zone and in the peripheral zone, was determined using a clonogenic assay for different radiation doses at the isocenter. Increased cell survival was observed inside the irradiation area for doses of 2, 10, and 20 Gy when nonirradiated cells were present at the periphery, while the cells at the periphery showed decreased survival compared to controls. Increased survival was also observed at the edge of the dose gradient zone for cells receiving 0.02 to 0.01 Gy when compared with cells at the periphery of the same flask, whatever the isocenter dose. These data are the first to report cell survival in the dose gradient zone. Radiotherapists must be aware of this nonlinearity in dose response.

Cortical areas involved in virtual movement of phantom limbs: comparison with normal subjects.

OBJECTIVE: To demonstrate that amputees performing "virtual" movements of their amputated limb activate cortical areas previously devoted to their missing limb, we studied amputees with functional magnetic resonance imaging (fMRI) and positron emission tomographic (PET) scans and compared the results with those of normal volunteers performing imaginary movements during fMRI acquisitions. METHODS: Ten amputees (age range, 33-92 yr; average age, 49 yr; six men and four women; eight upper-limb and two lower-limb amputations) able to move their phantom limb at will were studied by fMRI (all patients) and PET scan (seven patients). The time between amputation and fMRI and PET studies ranged from 1 to 27 years (average, 13 yr). Patients were asked to perform virtual movements of the amputated limb and normal movements of the contralateral normal limb according to the functional images acquisition procedure. Movements of the stump were also used to differentiate stump cortical areas from virtual movement-activated areas. Ten right-handed volunteers, age- and sex-matched to the amputees, were also studied by fMRI. All volunteers were asked to perform four tasks during their fMRI study: imaginary movements of their right arm (1 task) and foot (1 task) and real movements of their left arm (1 task) and foot (1 task). RESULTS: In amputees, virtual movements of the missing limbs produced contralateral primary sensorimotor cortex activation on both fMRI and PET scans. These activation areas, different from the stump activation areas, were similar in location to contralateral normal limb-activated areas. Quantitatively, in two amputees who claimed to be able to perform both slow and fast virtual movements, regional cerebral blood flow measured by PET scan in the precentral gyrus increased significantly during fast movements in comparison with slow virtual movements. In normal subjects, significant differences between real versus imaginary fMRI activations were found (for both foot and hand movements); imaginary right hand and foot tasks activated primarily the contralateral supplementary motor areas, with no significant activation detected in the contralateral precentral or postcentral gyri. CONCLUSION: Primary sensorimotor cortical areas can be activated by phantom-limb movements and thus can be considered functional for several years or decades after amputation. In this study, we found that the location of the activation of these areas is comparable to that of activations produced by normal movements in control subjects or in amputees.

Integration method of 3D MR spectroscopy into treatment planning system for glioblastoma IMRT dose painting with integrated simultaneous boost.

BACKGROUND: To integrate 3D MR spectroscopy imaging (MRSI) in the treatment planning system (TPS) for glioblastoma dose painting to guide simultaneous integrated boost (SIB) in intensity-modulated radiation therapy (IMRT). METHODS: For sixteen glioblastoma patients, we have simulated three types of dosimetry plans, one conventional plan of 60-Gy in 3D conformational radiotherapy (3D-CRT), one 60-Gy plan in IMRT and one 72-Gy plan in SIB-IMRT. All sixteen MRSI metabolic maps were integrated into TPS, using normalization with color-space conversion and threshold-based segmentation. The fusion between the metabolic maps and the planning CT scans were assessed. Dosimetry comparisons were performed between the different plans of 60-Gy 3D-CRT, 60-Gy IMRT and 72-Gy SIB-IMRT, the last plan was targeted on MRSI abnormalities and contrast enhancement (CE). RESULTS: Fusion assessment was performed for 160 transformations. It resulted in maximum differences <1.00 mm for translation parameters and ≤1.15° for rotation. Dosimetry plans of 72-Gy SIB-IMRT and 60-Gy IMRT showed a significantly decreased maximum dose to the brainstem (44.00 and 44.30 vs. 57.01 Gy) and decreased high dose-volumes to normal brain (19 and 20 vs. 23% and 7 and 7 vs. 12%) compared to 60-Gy 3D-CRT (p < 0.05). CONCLUSIONS: Delivering standard doses to conventional target and higher doses to new target volumes characterized by MRSI and CE is now possible and does not increase dose to organs at risk. MRSI and CE abnormalities are now integrated for glioblastoma SIB-IMRT, concomitant with temozolomide, in an ongoing multi-institutional phase-III clinical trial. Our method of MR spectroscopy maps integration to TPS is robust and reliable; integration to neuronavigation systems with this method could also improve glioblastoma resection or guide biopsies.

Modulation of behavior and cortical motor activity in healthy subjects by a chronic administration of a serotonin enhancer.

UNLABELLED: SSRIs are postulated to modulate motor behavior. A single dose of selective serotoninergic reuptake inhibitors (SSRIs) like fluoxetine, paroxetine, or fluvoxamine, has been shown to improve motor performance and efficiency of information processing for simple sensorimotor tasks in healthy subjects. At a cortical level, a single dose of SSRI was shown to induce a hyperactivation of the primary sensorimotor cortex (S1M1) involved in the movement (Loubinoux, I., Boulanouar, K., Ranjeva, J. P., Carel, C., Berry, I., Rascol, O., Celsis, P., and Chollet, F., 1999. Cerebral functional magnetic resonance imaging activation modulated by a single dose of the monoamine neurotransmission enhancers fluoxetine and fenozolone during hand sensorimotor tasks. J. Cereb. Blood Flow Metab. 19 1365--1375, Loubinoux, I., Pariente, J., Boulanouar, K., Carel, C., Manelfe, C., Rascol, O., Celsis, P., and Chollet, F., 2002. A Single Dose of Serotonin Neurotransmission Agonist Paroxetine Enhances Motor Output. A double-blind, placebo-controlled, fMRI study in healthy subjects. NeuroImage 15 26--36). Since SSRIs are usually given for several weeks, we assessed the behavioral and cerebral effects of a one-month chronic administration of paroxetine on a larger group. In a double-blind, placebo controlled and crossover study, 19 subjects received daily 20 mg paroxetine or placebo, respectively, over a period of 30 days separated by a wash-out period of 3 months. After each period, the subjects underwent an fMRI (active or passive movement, dexterity task, sensory discrimination task) and a behavioral evaluation. Concurrently, a TMS (transcranial magnetic stimulation) study was conducted (Gerdelat-Mas, A., Loubinoux, I., Tombari, D., Rascol, O., Chollet, F., Simonetta-Moreau, M., 2005. Chronic administration of selective serotonin re-uptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects. NeuroImage 27,314--322). RESULTS: On the one hand, paroxetine improved motor performances at the finger tapping test (P=0.02) without affecting choice reaction time, strength and dexterity significantly. Subjects were also faster in processing the spatial incongruency between a stimulus and the motor response (P=0.04). In order to differentiate behavioral components, a principal component analysis was performed on all motor tests, and several characteristics were differentiated: strength, speed, skill, attention, and motor response coding. Paroxetine would improve the efficiency of motor response coding (MANOVA on the factors; factor 3, P=0.01). On the other hand, the chronic administration induced a significant hypoactivation of S1M1 whatever the task: motor or sensory, simple or complex (random effect analysis, P<0.05). The hypoactivation correlated with the improvement of performances at the finger tapping test (P<0.05) suggesting more efficiency in cerebral motor processing. CONCLUSIONS: Our results showed a clear modulation of sensory and motor cerebral activation after a chronic paroxetine administration. An improvement in both behavior and cerebral efficiency was suggested. It could be hypothesized that monoamines, by an unspecific effect, may tune the response of pyramidal neurons to optimize performances.

A longitudinal fMRI study: in recovering and then in clinically stable sub-cortical stroke patients.

The aim of this 1-year longitudinal fMRI study was to compare hand motor activation patterns between cerebrovascular paretic patients with a subcortical infarction and healthy elderly subjects and to evaluate the changes between the subacute phase and the chronic phase of recovery. We studied eight right-handed patients with pure motor hemiparesis due to a single ischemic infarct of the corticospinal tract. Each patient underwent a first fMRI (E1) 20 +/- 9 days after stroke, a second (E2) after 4 months and a third (E3) 12 months after stroke. During each fMRI session, the patients performed an active motor task consisting of audio-paced (1 Hz) finger flexion-extension of the paretic hand and underwent a passive motor task consisting of flexion-extension of the paretic hand performed by an examiner. Data were analyzed with SPM99 (random effect analyses). Patients had recovered at E2, were stable between E2 and E3, but still experienced a hand weakness. Displacement of activation maxima coordinates in patients compared to healthy subjects suggested an early reorganization within the SMA and a secondary reorganization within the ipsilesional S1M1 at E2. The main differences between patients and healthy subjects were (1) recruitment of the posterior part of the cingulate cortex and SMA, (2) a general hyperactivation (except in the deefferented primary motor cortex) and (3) an evolution in the S1M1 activation from an early (20 days after stroke) contralesional hyperactivation to a later (4 months after stroke) ipsilesional hyperactivation concomitant to recovery. Changes in activation were confirmed by the passive task that involved no effort and little attention. Despite clinical stability, changes in brain processing seemed to occur between E2 and E3 corresponding to a normalization of ipsilesional S1M1 activation, a decrease of bilateral cerebellar activation, and a progressive increase in SII-BA 40 activity suggesting evolving compensatory networks to sustain recovery.

Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter.

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-monthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotropy were quantified over the segmented whole supratentorial white matter, with the indices of trace (Tr) and fractional anisotropy (FA). Results obtained in volunteers show the reproducibility of the method. Patients had higher trace and lower anisotropy than matched controls (P < 0.0001). Over the follow-up, both Tr and FA indicated a recovery after the acute phase in RRMS and a progressive shift towards abnormal values in SPMS. Although this result is not statistically significant, it suggests that DTI is sensitive to microscopic changes occurring in tissue of normal appearance in conventional images and could be useful for monitoring the course of the disease, even though it was unable to clearly distinguish between the various physiopathological processes involved.