Dual energy computed tomography cannot effectively differentiate between calcium pyrophosphate and basic calcium phosphate diseases in the clinical setting.

Background: Recent reports suggested that dual-energy CT (DECT) may help discriminate between different types of calcium phosphate crystals in vivo, which would have important implications for the characterization of crystal deposition occurring in osteoarthritis. Purpose: Our aim was to test the hypothesis that DECT can effectively differentiate basic calcium phosphate (BCP) from calcium pyrophosphate (CPP) deposition diseases. Methods: Discarded tissue after total knee replacement specimens in a 71 year-old patient with knee osteoarthritis and chondrocalcinosis was scanned using DECT at standard clinical parameters. Specimens were then examined on light microscopy which revealed CPP deposition in 4 specimens (medial femoral condyle, lateral tibial plateau and both menisci) without BCP deposition. Regions of interest were placed on post-processed CT images using Rho/Z maps (Syngo.via, Siemens Healthineers, VB10B) in different areas of CPP deposition, trabecular bone BCP (T-BCP) and subchondral bone plate BCP (C-BCP). Results: Dual Energy Index (DEI) of CPP was 0.12 (SD â€‹= â€‹0.02) for reader 1 and 0.09 (SD â€‹= â€‹0.03) for reader 2, The effective atomic number (Zeff) of CPP was 10.83 (SD â€‹= â€‹0.44) for reader 1 and 10.11 (SD â€‹= â€‹0.66) for reader 2. Nearly all DECT parameters of CPP were higher than those of T-BCP, lower than those of C-BCP, and largely overlapping with Aggregate-BCP (aggregate of T-BCP and C-BCP). Conclusion: Differentiation of different types of calcium crystals using DECT is not feasible in a clinical setting.

Near-Infrared Imaging of Indocyanine Green Identifies Novel Routes of Lymphatic Drainage from Metacarpophalangeal Joints in Healthy Human Hands.

Background: Collecting lymphatic vessel (CLV) dysfunction has been implicated in various diseases, including rheumatoid arthritis (RA). RA patients with active hand arthritis exhibit significantly reduced lymphatic clearance of the web spaces adjacent to the metacarpophalangeal (MCP) joints and a reduction in total and basilic-associated CLVs on the dorsal surface of the hand by near-infrared (NIR) imaging of indocyanine green (ICG). In this pilot study, we assessed direct lymphatic drainage from MCP joints and aimed to visualize the total lymphatic anatomy using novel dual-agent relaxation contrast magnetic resonance lymphography (DARC-MRL) in the upper extremity of healthy human subjects. Methods and Results: Two healthy male subjects >18 years old participated in the study. We performed NIR imaging along with conventional- or DARC-MRL following intradermal web space and intra-articular MCP joint injections. ICG (NIR) or gadolinium (Gd) (MRL) was administered to visualize the CLV anatomy of the upper extremity. Web space draining CLVs were associated with the cephalic side of the antecubital fossa, while MCP draining CLVs were localized to the basilic side of the forearm by near-infrared indocyanine green imaging. The DARC-MRL methods used in this study did not adequately nullify the contrast in the blood vessels, and limited Gd-filled CLVs were identified. Conclusion: MCP joints predominantly drain into basilic CLVs in the forearm, which may explain the reduction in basilic-associated CLVs in the hands of RA patients. Current DARC-MRL techniques show limited identification of healthy lymphatic structures, and further refinement in this technique is necessary. Clinical trial registration number: NCT04046146.

System-specific evaluation of the dual flip angle MRI technique for quantitative T1 measurement.

PURPOSE: To investigate if the accuracy of the dual flip angle (DFA) technique for T1 measurement is affected by the system-specific RF excitation performance. METHODS: A T1 phantom, made of 12 vials of unique T1 value ranging approximately from 200 ms to 2000 ms, was built and tested on seven different clinical scanners. For each experiment, the reference T1 of each vial was obtained by the inversion recovery-based technique, and the DFA technique was applied repeatedly with several flip angle (FA) pairs conventionally proposed as optimal. The accuracy of the DFA technique for each FA pair was then evaluated by comparing the measured T1 values for the vials to the references. Any variation of the accuracy was then evaluated across different FA pairs, and across different MRI systems. To improve accuracy with a selected FA pair, the signal ratio (SR) curve, obtained from the phantom, was utilized in a calibration strategy of the DFA technique. RESULTS: When combined for all the vials, the average ratio of the measured T1 to the reference generally increased as the FA pair window gradually slid from the smaller to the larger FA values. Furthermore, among several optimal FA pairs, the pair of the best accuracy varied slightly by the MRI system. The accuracy for any FA pair could be improved when the calibration strategy was utilized. CONCLUSIONS: The RF excitation performance may vary by the specific FA pair and by the specific MRI system, influencing the accuracy of the DFA technique. The system-specific evaluation, and, if needed, its calibration, would help improve the accuracy of the DFA technique.

MR image-based synthetic CT for IMRT prostate treatment planning and CBCT image-guided localization.

The purpose of this study was to propose and evaluate a method of creating a synthetic CT (S-CT) from MRI simulation for dose calculation and daily CBCT localization. A pair of MR and CT images was obtained in the same day from each of 10 prostate patients. The pair of MR and CT images was preregistered using the deformable image registration (DIR). Using the corresponding displacement vector field (atlas-DVF), the CT image was deformed to the MR image to create an atlas MR-CT pair. Regions of interest (ROI) on the atlas MR-CT pair were delineated and used to create atlas-ROI masks. 'Leave-one-out' test (one pair of MR and CT was used as subject-MR and subject-CT for evaluation, and the remaining 9 pairs were in the atlas library) was performed. For a subject-MR, autosegmentation and DVFs were generated using DIR between the subject-MR and the 9 atlas-MRs. An S-CT was then generated using the corresponding 9 paired atlas-CTs, the 9 atlas-DVFs and the corresponding atlas-ROI masks. The total 10 S-CTs were evaluated using the Hounsfield unit (HU), the calculated dose distribution, and the auto bony registration to daily CBCT images with respect to the 10 subject-CTs. HU differences (mean ± STD) were (2.4 ± 25.23), (1.18 ± 39.49), (32.46 ± 81.9), (0.23 ± 40.13), and (3.74 ± 144.76) for prostate, bladder, rectal wall, soft tissue outside all ROIs, and bone, respectively. The discrepancy of dose-volume param-eters calculated using the S-CT for treatment planning was small (≤ 0.22% with 95% confidence). Gamma pass rate (2% & 2 mm) was higher than 99.86% inside PTV and 98.45% inside normal structures. Using the 10 S-CTs as the reference CT for daily CBCT localization achieved the similar results compared to using the subject-CT. The translational vector differences were within 1.08 mm (0.37 ± 0.23 mm), and the rotational differences were within 1.1° in all three directions. S-CT created from a simulation MR image using the proposed approach with the preconstructed atlas library can replace the planning CT for dose calculation and daily CBCT image guidance.

Segmentation of fat in MRI using a preparatory pair of rectangular RF pulses of opposite direction.

A radiofrequency (RF) pulse-based MRI method is introduced as a novel fat (or water) segmentation method that, unlike the mostly used Dixon's method, does not depend on the echo times. A pair of rectangular RF pulses of opposite direction, when the duration of its rectangular pulse and the off-resonance of its carrier frequency are set to specific values, is proposed as a preparatory RF pulse to be used for the quantitative fat segmentation. The optimal duration of its rectangular pulse and its specific off-resonance were first determined theoretically. Then, such pair of rectangular pulses of opposite direction (PROD pulse) was applied in imaging a few phantoms and volunteers. During the imaging experiments, MRI images were dynamically acquired with the PROD pulse while its carrier frequency was varied in a predefined off-resonance range. By analyzing the dynamically acquired signal changes, the theoretical properties of the PROD pulse were confirmed and the utility of the PROD pulse for the fat segmentation was verified. All MRI scans were performed in a clinical 3T system. The PROD pulse, if the duration of each rectangular pulse was set to 1.66ms and its carrier frequency was set to a specific off-resonance (e.g. ±223.5Hz, or -670.5Hz) in 3T, was effective in optimally modulating MRI signals to be used for the fat-water segmentation. Therefore, the PROD pulse can successfully be used as a preparatory RF pulse in MRI to achieve effective fat (or water) segmentation in MRI.

Effects of spin-lock field direction on the quantitative measurement of spin-lattice relaxation time constant in the rotating frame (T1ρ) in a clinical MRI system.

PURPOSE: To investigate whether the direction of spin-lock field, either parallel or antiparallel to the rotating magnetization, has any effect on the spin-lock MRI signal and further on the quantitative measurement of T1ρ, in a clinical 3 T MRI system. METHODS: The effects of inverted spin-lock field direction were investigated by acquiring a series of spin-lock MRI signals for an American College of Radiology MRI phantom, while the spin-lock field direction was switched between the parallel and antiparallel directions. The acquisition was performed for different spin-locking methods (i.e., for the single- and dual-field spin-locking methods) and for different levels of clinically feasible spin-lock field strength, ranging from 100 to 500 Hz, while the spin-lock duration was varied in the range from 0 to 100 ms. RESULTS: When the spin-lock field was inverted into the antiparallel direction, the rate of MRI signal decay was altered and the T1ρ value, when compared to the value for the parallel field, was clearly different. Different degrees of such direction-dependency were observed for different spin-lock field strengths. In addition, the dependency was much smaller when the parallel and the antiparallel fields are mixed together in the dual-field method. CONCLUSIONS: The spin-lock field direction could impact the MRI signal and further the T1ρ measurement in a clinical MRI system.

Measurement of cardiac output from dynamic pulmonary circulation time CT.

PURPOSE: To introduce a method of estimating cardiac output from the dynamic pulmonary circulation time CT that is primarily used to determine the optimal time window of CT pulmonary angiography (CTPA). METHODS: Dynamic pulmonary circulation time CT series, acquired for eight patients, were retrospectively analyzed. The dynamic CT series was acquired, prior to the main CTPA, in cine mode (1 frame/s) for a single slice at the level of the main pulmonary artery covering the cross sections of ascending aorta (AA) and descending aorta (DA) during the infusion of iodinated contrast. The time series of contrast changes obtained for DA, which is the downstream of AA, was assumed to be related to the time series for AA by the convolution with a delay function. The delay time constant in the delay function, representing the average time interval between the cross sections of AA and DA, was determined by least square error fitting between the convoluted AA time series and the DA time series. The cardiac output was then calculated by dividing the volume of the aortic arch between the cross sections of AA and DA (estimated from the single slice CT image) by the average time interval, and multiplying the result by a correction factor. RESULTS: The mean cardiac output value for the six patients was 5.11 (l/min) (with a standard deviation of 1.57 l/min), which is in good agreement with the literature value; the data for the other two patients were too noisy for processing. CONCLUSIONS: The dynamic single-slice pulmonary circulation time CT series also can be used to estimate cardiac output.

Consideration of optimal time window for Pittsburgh compound B PET summed uptake measurements.

UNLABELLED: The standardized uptake value ratio (SUVR, or summed tissue ratio) has been used effectively in Pittsburgh compound B (PiB) PET studies to distinguish subjects who have significant amyloid-beta deposition in their brain from those who do not. Relative to quantitative measurements, advantages of the SUVR are improved study feasibility and low test-retest variation; disadvantages include inherent bias (PiB retention overestimation) and potential for time-varying outcomes. The PiB SUVR has proven to be highly correlated with quantitative outcomes and to allow reliable detection of significant group differences (or effective contrasts). In this work, regional PiB SUVRs were examined across 9 time windows to select the window that provided the best trade-offs between bias, correlation, and effective contrast. METHODS: A total of 40 dynamic PiB PET studies were performed on controls (n = 16), patients with Alzheimer disease (AD; n = 11), and patients with mild cognitive impairment (MCI; n = 13) (555 MBq [15 mCi], 90-min scan, and arterial blood sampling). The SUVR was computed for five 20-min and four 30-min windows that spanned the 30- to 90-min postinjection period. The SUVRs were compared with Logan graphical distribution volume ratio (DVR) measurements (35-90 min), determined with arterial blood as input and without arterial blood as input (cerebellum as reference). RESULTS: Greater correlation and more bias were generally observed for the SUVR measurement at later times than at earlier times (relative to DVR). The effective contrast between the control and AD PiB SUVRs was slightly better for earlier data than for later data. The temporal dynamics of the SUVR measurement indicated greater stability in the measurement at 40 min after injection. CONCLUSION: The 50- to 70-min time window provided a good compromise between physiologic validity, stability, sensitivity, and clinical feasibility across the control, MCI, and AD subject data examined in this study. The 40- to 60-min period demonstrated many advantages and should be used in studies limited by low injected dose. Although more biased than the 40- to 60-min SUVR, the 50- to 70-min SUVR was thought to be optimal because of greater measurement stability, which may prove to be important for longitudinal multisite studies performed in control, MCI, and AD subjects that are not dose-limited.

Cerebral oxygen delivery by liposome-encapsulated hemoglobin: a positron-emission tomographic evaluation in a rat model of hemorrhagic shock.

Liposome-encapsulated Hb (LEH) is being developed as an artificially assembled, low-toxicity, and spatially isolated Hb-based oxygen carrier (HBOC). Standard methods of evaluating oxygen carriers are based on surrogate indicators of physiology in animal models of shock. Assessment of actual delivery of oxygen by HBOCs and resultant improvement in oxygen metabolism at the tissue level has been a technical challenge. In this work, we report our findings from 15O-positron emission tomographic (15O-PET) evaluation of LEH in a rat model of 40% hypovolemic shock. In vitro studies showed that PEGylated LEH formulation containing approximately 7.5% Hb and consisting of neutral lipids (distearoylphosphatidylcholine:cholesterol:alpha-tocopherol, 51.4:46.4:2.2) efficiently picks up 15O-labeled oxygen gas. The final preparation of LEH contained 5% human serum albumin to provide oncotic pressure. Cerebral PET images of anesthetized rats inhaling 15O-labeled O2 gas showed efficient oxygen-carrying and delivery capacity of LEH formulation. From the PET images, we determined cerebral metabolic rate of oxygen (CMR(O2)) as a direct indicator of oxygen-carrying capacity of LEH as well as oxygen delivery and metabolism in rat brain. Compared with control fluids [saline and 5% human serum albumin (HSA)], LEH significantly improved CMR(O2) to approximately 80% of baseline level. Saline and HSA resuscitation could not improve hypovolemia-induced decrease in CMR(O2). On the other hand, resuscitation of shed blood was the most efficient in restoring oxygen metabolism. The results suggest that 15O-PET technology can be successfully employed to evaluate potential oxygen carriers and blood substitutes and that LEH resuscitation in hemorrhage enhances oxygen delivery to the cerebral tissue and improves oxygen metabolism in brain.

Quantitative measurement of oxygen metabolic rate in the rat brain using microPET imaging of briefly inhaled 15O-labelled oxygen gas.

OBJECTIVE: The quantitative measurement of cerebral metabolic rate of oxygen (CMRO(2)) for rats using positron emission tomography (PET) has been technically difficult. The present study was performed to provide a technique to measure CMRO(2) for rats using a dedicated animal PET technique. METHODS: CMRO(2) in the rat brain was quantitatively measured under alpha-chloralose anaesthesia (30 mg . kg(-1) . h(-1), intravenous infusion) using a PET imaging technique. In our experiment, the (15)O-labelled gas tracer (O(15)O) was administered by a bolus insufflation into the lung through a surgically placed cannula in the trachea. The tracer distribution was then dynamically imaged using the microPET. Unlike other conventional PET methods in which a series of arterial blood samples need to be withdrawn for the measurement of an arterial input function, no arterial blood sampling was employed. Instead, the heart was scanned in dynamic mode at the same time of imaging the brain, and the region of interest drawn over the heart was analysed to obtain an arterial input function. RESULTS: The CMRO(2) value (micromol . 100 g(-1) . min(-1)) from 10 rats was 208 +/- 15 (mean +/- SD). CONCLUSIONS: Our results suggest that the microPET-based CMRO(2) measurement in the rat brain combined with a non-invasive measurement of arterial input function is promising, especially for many applications involving small animals in which repeated measurements of absolute CMRO(2) need to be performed.

Non-invasive quantification of cerebral blood flow for rats by microPET imaging of 15O labelled water: the application of a cardiac time-activity curve for the tracer arterial input function.

OBJECTIVE: In-vivo quantitative cerebral blood flow (CBF) measurement using positron emission tomography (PET) has typically employed invasive arterial blood sampling procedure to determine the arterial input function (AIF). The present study was performed to provide a non-invasive quantitative CBF measurement technique for rats using a dedicated animal PET. METHODS: CBF was measured in 10 male rats (Fischer 344, 247-290 g) under alpha-chloralose anesthesia (30 mg x kg . h, intravenous infusion) by dynamic PET imaging employing the intravenous bolus injection of H2(15)O. Unlike other conventional PET methods, no arterial blood sampling was employed. Instead, a cardiac time-activity curve (TAC) obtained from the dynamic PET imaging was used to determine the AIF. For the validation of this technique, CBF was also measured by calculating the washout rate of the tracer (H2(15)O) following an intracarotid bolus injection. CBF measurements by two independent methods were done while modulating and maintaining the body temperature at two different levels (32+/-1 and 37+/-1 degrees C by the rectal temperature). Two methods were compared by the linear regression analysis. RESULTS: CBF (ml x 100 g x min) values (mean+/-SD) were 45.2+/-6.05 (intravenous) and 47.4+/-8.64 (intracarotid) at the hypothermic condition (32 degrees C), and 55.1+/-4.88 (intravenous) and 54.4+/-4.60 (intracarotid) at the normothermic condition (37 degrees C). There was a good agreement between the two methods (r=0.70). CONCLUSIONS: Our cardiac TAC analysis technique for small animals can be used for the non-invasive quantification of CBF using the PET-based in-vivo imaging technique.

Iterative temporal clustering analysis for the detection of multiple response peaks in fMRI.

The temporal clustering analysis (TCA) is a novel and effective technique for obtaining brain activation maps when the timing and location of the activation are completely unknown. Performing the TCA method once can only detect the largest peak of the activation time windows well, if multiple response peaks at the same location of the brain occur. However, this limitation can be removed by using a TCA method in an iterative way in order for the smaller peaks to be detected. Our in vivo fMRI experiments with event-related visual tasks have demonstrated this ability.

Improved detection of time windows of brain responses in fMRI using modified temporal clustering analysis.

Temporal clustering analysis (TCA) has been proposed recently as a method to detect time windows of brain responses in functional MRI (fMRI) studies when the timing and location of the activation are completely unknown. Modifications to the TCA technique are introduced in this report to further improve the sensitivity in detecting brain activation. The modified TCA is based on the integrated signal intensity of a temporal cluster at each time point, while the original TCA is based only on the size of a temporal cluster at each time point. A temporal cluster at each time point is defined, in both TCA methods, as a group of pixels reaching their maximum (or minimum) values at the same time. Both computer simulation and in vivo fMRI experiments have been performed. Compared with the original TCA, the modified TCA shows a significant improvement in the sensitivity to detect activation peaks for determining time windows of brain responses.