PET/MRI Assessment of Acute Cardiac Inflammation 1 Month After Left-Sided Breast Cancer Radiation Therapy.

Our purpose was to investigate the utility of 18F-FDG PET/MRI and serial blood work to detect early inflammatory responses and cardiac functionality changes at 1 mo after radiation therapy (RT) in patients with left-sided breast cancer. Methods: Fifteen left-sided breast cancer patients who enrolled in the RICT-BREAST study underwent cardiac PET/MRI at baseline and 1 mo after standard RT. Eleven patients received deep-inspiration breath-hold RT, whereas the others received free-breathing RT. A list-mode 18F-FDG PET scan with glucose suppression was acquired. Myocardial inflammation was quantified by the change in 18F-FDG SUVmean (based on body weight) and analyzed on the basis of the myocardial tissue associated with the left anterior descending, left circumflex, or right coronary artery territories. MRI assessments, including left ventricular functional and extracellular volumes (ECVs), were extracted from T1 (before and during a constant infusion of gadolinium) and cine images, respectively, acquired simultaneously during the PET acquisition. Cardiac injury and inflammation biomarker measurements of high-sensitivity troponin T, high-sensitivity C-reactive protein, and erythrocyte sedimentation rate were measured at the 1-mo follow-up and compared with preirradiation values. Results: At the 1-mo follow-up, a significant increase (10%) in myocardial SUVmean in left anterior descending segments (P = 0.04) and ECVs in slices at the apex (6%) and base (5%) was detected (P ≤ 0.02). Further, a significant reduction in left ventricular stroke volume (-7%) was seen (P < 0.02). No significant changes in any circulating biomarkers were seen at follow-up. Conclusion: Myocardial 18F-FDG uptake and functional MRI, including stroke volume and ECVs, were sensitive to changes at 1 mo after breast cancer RT, with findings suggesting an acute cardiac inflammatory response to RT.

Assessment of left atrial fibrosis progression in canines following rapid ventricular pacing using 3D late gadolinium enhanced CMR images.

BACKGROUND: Atrial fibrillation (AF) is associated with extracellular matrix (ECM) remodelling and often coexists with myocardial fibrosis (MF); however, the causality of these conditions is not well established. OBJECTIVE: We aim to corroborate AF to MF causality by quantifying left atrial (LA) fibrosis in cardiac magnetic resonance (CMR) images after persistent rapid ventricular pacing and subsequent AF using a canine model and histopathological validation. METHODS: Twelve canines (9 experimental, 3 control) underwent baseline 3D LGE-CMR imaging at 3T followed by insertion of a pacing device and 5 weeks of rapid ventricular pacing to induce AF (experimental) or no pacing (control). Following the 5 weeks, pacing devices were removed to permit CMR imaging followed by excision of the hearts and histopathological imaging. LA myocardial segmentation was performed manually at baseline and post-pacing to permit volumetric %MF quantification using the image intensity ratio (IIR) technique, wherein fibrosis was defined as pixels > mean LA myocardium intensity + 2SD. RESULTS: Volumetric %MF increased by an average of 2.11 ± 0.88% post-pacing in 7 of 9 experimental dogs. While there was a significant difference between paired %MF measurements from baseline to post-pacing in experimental dogs (P = 0.019), there was no significant change in control dogs (P = 0.019 and P = 0.5, Wilcoxon signed rank tests). The median %MF for paced animals was significantly greater than that of non-paced dogs at the 5-week post-insertion time point (P = 0.009, Mann Whitney U test). Histopathological imaging yielded an average %MF of 19.42 ± 4.80% (mean ± SD) for paced dogs compared to 1.85% in one control dog. CONCLUSION: Persistent rapid ventricular pacing and subsequent AF leads to an increase in LA fibrosis volumes measured by the IIR technique; however, quantification is limited by inherent image acquisition parameters and observer variability.

Assessment of intramyocardial hemorrhage with dark-blood T2*-weighted cardiovascular magnetic resonance.

BACKGROUND: Intramyocardial hemorrhage (IMH) within myocardial infarction (MI) is associated with major adverse cardiovascular events. Bright-blood T2*-based cardiovascular magnetic resonance (CMR) has emerged as the reference standard for non-invasive IMH detection. Despite this, the dark-blood T2*-based CMR is becoming interchangeably used with bright-blood T2*-weighted CMR in both clinical and preclinical settings for IMH detection. To date however, the relative merits of dark-blood T2*-weighted with respect to bright-blood T2*-weighted CMR for IMH characterization has not been studied. We investigated the diagnostic capacity of dark-blood T2*-weighted CMR against bright-blood T2*-weighted CMR for IMH characterization in clinical and preclinical settings. MATERIALS AND METHODS: Hemorrhagic MI patients (n = 20) and canines (n = 11) were imaged in the acute and chronic phases at 1.5 and 3 T with dark- and bright-blood T2*-weighted CMR. Imaging characteristics (Relative signal-to-noise (SNR), Relative contrast-to-noise (CNR), IMH Extent) and diagnostic performance (sensitivity, specificity, accuracy, area-under-the-curve, and inter-observer variability) of dark-blood T2*-weighted CMR for IMH characterization were assessed relative to bright-blood T2*-weighted CMR. RESULTS: At both clinical and preclinical settings, compared to bright-blood T2*-weighted CMR, dark-blood T2*-weighted images had significantly lower SNR, CNR and reduced IMH extent (all p < 0.05). Dark-blood T2*-weighted CMR also demonstrated weaker sensitivity, specificity, accuracy, and inter-observer variability compared to bright-blood T2*-weighted CMR (all p < 0.05). These observations were consistent across infarct age and imaging field strengths. CONCLUSION: While IMH can be visible on dark-blood T2*-weighted CMR, the overall conspicuity of IMH is significantly reduced compared to that observed in bright-blood T2*-weighted images, across infarct age in clinical and preclinical settings at 1.5 and 3 T. Hence, bright-blood T2*-weighted CMR would be preferable for clinical use since dark-blood T2*-weighted CMR carries the potential to misclassify hemorrhagic MIs as non-hemorrhagic MIs.

DCE-MRI assessment of response to neoadjuvant SABR in early stage breast cancer: Comparisons of single versus three fraction schemes and two different imaging time delays post-SABR.

PURPOSE: To determine the effect of dose fractionation and time delay post-neoadjuvant stereotactic ablative radiotherapy (SABR) on dynamic contrast-enhanced (DCE)-MRI parameters in early stage breast cancer patients. MATERIALS AND METHODS: DCE-MRI was acquired in 17 patients pre- and post-SABR. Five patients were imaged 6-7 days post-21 Gy/1fraction (group 1), six 16-19 days post-21 Gy/1fraction (group 2), and six 16-18 days post-30 Gy/3 fractions every other day (group 3). DCE-MRI scans were performed using half the clinical dose of contrast agent. Changes in the surrounding tissue were quantified using a signal-enhancement threshold metric that characterizes changes in signal-enhancement volume (SEV). Tumour response was quantified using Ktrans and ve (Tofts model) pre- and post-SABR. Significance was assessed using a Wilcoxin signed-rank test. RESULTS: All group 1 and 4/6 group 2 patients' SEV increased post-SABR. All group 3 patients' SEV decreased. The mean Ktrans increased for group 1 by 76% (p = 0.043) while group 2 and 3 decreased 15% (p = 0.028) and 34% (p = 0.028), respectively. For ve, there was no significant change in Group 1 (p = 0.35). Groups 2 showed an increase of 24% (p = 0.043), and Group 3 trended toward an increase (23%, p = 0.08). CONCLUSION: Kinetic parameters measured 2.5 weeks post-SABR in both single fraction and three fraction groups were indicative of response but only the single fraction protocol led to enhancement in the surrounding tissue. Our results also suggest that DCE-MRI one-week post-SABR may be too early for response assessment, at least for single fraction SABR, whereas 2.5 weeks appears sufficiently long to minimize confounding acute effects.

Accurate needle-free assessment of myocardial oxygenation for ischemic heart disease in canines using magnetic resonance imaging.

Myocardial oxygenation-the ability of blood vessels to supply the heart muscle (myocardium) with oxygen-is a critical determinant of cardiac function. Impairment of myocardial oxygenation is a defining feature of ischemic heart disease (IHD), which is caused by pathological conditions that affect the blood vessels supplying oxygen to the heart muscle. Detecting altered myocardial oxygenation can help guide interventions and prevent acute life-threatening events such as heart attacks (myocardial infarction); however, current diagnosis of IHD relies on surrogate metrics and exogenous contrast agents for which many patients are contraindicated. An oxygenation-sensitive cardiac magnetic resonance imaging (CMR) approach used previously to demonstrate that CMR signals can be sensitized to changes in myocardial oxygenation showed limited ability to detect small changes in signals in the heart because of physiologic and imaging noise during data acquisition. Here, we demonstrate a CMR-based approach termed cfMRI [cardiac functional magnetic resonance imaging (MRI)] that detects myocardial oxygenation. cfMRI uses carbon dioxide for repeat interrogation of the functional capacity of the heart's blood vessels via a fast MRI approach suitable for clinical adoption without limitations of key confounders (cardiac/respiratory motion and heart rate changes). This method integrates multiple whole-heart images within a computational framework to reduce noise, producing confidence maps of alterations in myocardial oxygenation. cfMRI permits noninvasive monitoring of myocardial oxygenation without requiring ionizing radiation, contrast agents, or needles. This has the potential to broaden our ability to noninvasively identify IHD and a diverse spectrum of heart diseases related to myocardial ischemia.

Assessment of a novel 32-channel phased array for cardiovascular hybrid PET/MRI imaging: MRI performance.

BACKGROUND: Cardiovascular imaging using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI) requires a radio frequency phased array resonator capable of high acceleration factors in order to achieve the shortest breath-holds while maintaining optimal MRI signal-to-noise ratio (SNR) and minimum PET photon attenuation. To our knowledge, the only two arrays used today for hybrid PET/MRI cardiovascular imaging are either incapable of achieving high acceleration or affect the PET photon count greatly. PURPOSE: This study is focused on the evaluation of the MRI performance of a novel third-party prototype 32-channel phased array designed for simultaneous PET/MRI cardiovascular imaging. The study compares the quality parameters of MRI parallel imaging, such as g-factor, noise correlation coefficients, and SNR, to the conventional arrays (mMR 12-channel and MRI-only 32-channel) currently used with hybrid PET/MRI systems. The quality parameters of parallel imaging were estimated for multiple acceleration factors on a phantom and three healthy volunteers. Using a Germanium-68 (Ge-68) phantom, preliminary measurements of PET photon attenuation caused by the novel array were briefly compared to the photon counts produced from no-array measurements. RESULTS: The global mean of the g-factor and SNRg produced by the novel 32-channel PET/MRI array were better than those produced by the MRI-only 32-channel array by 5% or more. The novel array has resulted in MRI SNR improvements of > 30% at all acceleration factors, in comparison to the mMR12-channel array. Preliminary evaluation of PET transparency showed less than 5% photon attenuation caused by both anterior and posterior parts of the novel array. CONCLUSIONS: The MRI performance of the novel PET/MRI 32-channel array qualifies it to be a viable alternative to the conventional arrays for cardiovascular hybrid PET/MRI. A detailed evaluation of the novel array's PET performance remains to be conducted, but cursory assessment promises significantly reduced attenuation.

Description and assessment of a registration-based approach to include bones for attenuation correction of whole-body PET/MRI.

PURPOSE: Attenuation correction for whole-body PET/MRI is challenging. Most commercial systems compute the attenuation map from MRI using a four-tissue segmentation approach. Bones, the most electron-dense tissue, are neglected because they are difficult to segment. In this work, the authors build on this segmentation approach by adding bones using a registration technique and assessing its performance on human PET images. METHODS: Twelve oncology patients were imaged with FDG PET/CT and MRI using a Turbo-FLASH pulse sequence. A database of 121 attenuation correction quality CT scans was also collected. Each patient MRI was compared to the CT database via weighted heuristic measures to find the "most similar" CT in terms of body geometry. The similar CT was aligned to the MRI with a deformable registration method. Two MRI-based attenuation maps were computed. One was a standard four-tissue segmentation (air, lung, fat, and lean tissue) using basic image processing techniques. The other was identical, except the bones from the aligned CT were added. The PET data were reconstructed with the patient's CT-based attenuation map (the silver standard) and both MRI-based attenuation maps. The relative errors of the MRI-based attenuation corrections were computed in 14 standardized volumes of interest, in lesions, and over whole tissues. The squared Pearson correlation coefficient was also calculated over whole tissues. Statistical testing was done with ANOVAs and paired t-tests. RESULTS: The MRI-based attenuation correction ignoring bone had relative errors ranging from -37% to -8% in volumes of interest containing bone. By including bone, the magnitude of the relative error was reduced in all cases (p<0.001), ranging from -3% to 4%. Further, the relative error in volumes of interest adjacent to bone was improved from a mean of -7.5% to 2% (p<0.001). In the other seven volumes of interest, including bone reduced the magnitude of relative error in three cases (p<0.001), had no effect in three cases, and increased relative error in one case. There was no statistically significant difference in the relative error in lesions. Over whole tissues, including bone slightly increased relative error in lung from 7.7% to 8.0% (p=0.002), in fat from 8.5% to 9.2% (p<0.001), and in lean tissue from -2.1% to 2.6% (p<0.001), but reduced the magnitude of relative error in bone from -14.6% to 1.3% (p<0.001). The correlation coefficient was essentially unchanged in all tissues regardless of whether bone was included or not. CONCLUSIONS: The approach to include bones in MRI-based attenuation maps described in this work improves quantification of whole-body PET images in and around bony anatomy. The reduction in error is often large (tens of percents), and could alter image interpretation and subsequent patient care. Changes in other parts of the PET image are minimal and likely not of clinical significance.

Assessment of genetic damage in peripheral blood of human volunteers exposed (whole-body) to a 200 muT, 60 Hz magnetic field.

AIM: To investigate the extent of damage in nucleated cells in peripheral blood of healthy human volunteers exposed to a whole-body 60 Hz, 200 microT magnetic field. MATERIALS AND METHODS: In this study, 10 male and 10 female healthy human volunteers received a 4 h whole-body exposure to a 200 microT, 60 Hz magnetic field. In addition, five males and five females were treated in a similar fashion, but were exposed to sham conditions. For each subject, a blood sample was obtained prior to the exposure period and aliquots were used as negative- (pre-exposure) and positive- [1.5 Gray (Gy) (60)Cobalt ((60)Co) gamma-irradiation] controls. At the end of the 4 h exposure period, a second blood sample was obtained. The extent of DNA damage was assessed in peripheral human blood leukocytes from all samples using the alkaline comet assay. To detect possible clastogenic effects, the incidence of micronuclei was assessed in phytohemagglutinin (PHA)-stimulated lymphocytes using the cytokinesis-block micronucleus assay. RESULTS: There was no evidence of either increased DNA damage, as indicated by the alkaline comet assay, or increased incidence of micronuclei (MN) in the magnetic field exposed group. However, an in vitro exposure of 1.5 Gy gamma-irradiation caused a significant increase in both DNA damage and MN induction. CONCLUSIONS: This study found no evidence that an acute, whole-body exposure to a 200 microT, 60 Hz magnetic field for 4 hours could cause DNA damage in human blood.

The assessment of myocardial viability: a review of current diagnostic imaging approaches.

The management of patients with coronary artery disease, both in the post-infarction setting, and in patients with chronic advanced left ventricular (LV) dysfunction, is complicated by the presence of both reversibly damaged and infarcted myocardium. Although acute revascularization with thrombolytic therapy and percutaneous angioplasty have served to reduce the overall mortality from myocardial infarction, the ability to predict whether or not dysfunctional myocardium will recoverfollowing revascularization presents the clinician with a serious challenge. The success of revascularization, both on improvement of LV function, and short and long-term prognosis, depends on both the existence and extent of viable but dysfunctional myocardium present, as there is little to be gained from revascularizing a territory consisting exclusively of scar. There is a clear demand for procedures that can identify reversible asynergy prospectively and thus deliver the information that is needed for clinical decision-making. The objective of this review is to summarize the diagnostic tools that are currently availablefor the identification of reversible injury (ie., stunned or hibernating myocardium). The relative merits of echocardiography, nuclear medicine imaging, and magnetic resonance imaging are discussed in detail. Within the discussion of each modality, special attention is paid to the more recent innovations that have arisen to enhance the diagnostic and prognostic value of older approaches. Cost, availability, and local expertise will always affect the clinical popularity of a given diagnostic approach. However, the overriding conclusion that emerges from this review is that the future "techniques of choice" will be those that can reliably predict and quantify the extent of potential functional recovery.