Fluorescent probes are useful tools for studying chemical biology, available in a wide variety of colours and applicable to different biochemical processes. One of their hallmarks is the ability to tune their chemistry and allow them to selectively “turn on” in response to different biomolecular targets of interest. However, fluorescence is largely limited by shallow tissue depth of penetration. Magnetic resonance imaging (MRI) can overcome the depth of penetration limitations to better map these biochemical processes and mechanisms with contrast agents. Chemical exchange saturation transfer (CEST) MRI is an alternative method to generating contrast in MR imaging that, like fluorescence, can provide multiplexed imaging by varying the chemical shift of the exchangeable proton on the contrast agent. Previously, a paramagnetic CEST agent containing two tetramethylpiperidinyloxyl (TEMPO) moieties was shown to reduce the CEST signal of a lanthanide complex due to T1 shortening effects on bulk water. Herein, we present a probe design strategy capable of suppressing the diamagnetic CEST (diaCEST) signal with the use of an N-hydroxy piperidine moiety. This discovery that N-hydroxy piperidine is capable of suppressing the diaCEST signal was applied to the study the activity of fibroblast activation protein-α (FAP). FAP is an enzyme involved in maintaining the tumour environment and its interactions can help understand tumour development, invasion and metastasis.

There is increasing acknowledgement that problematic interpersonal relationships and negative emotions are key factors in the development and maintenance of various forms of psychopathology. Emotionally Focused Therapy (EFT) for couples centers on changing attachment behaviours as a means to improve distressed relationships by helping partners access underlying emotions and foster positive interactions that promote accessibility and trust. EFT is a highly effective therapeutic approach that encourages the development of adaptive emotion regulation observed in secure attachment. The development and emergence of non-invasive neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), provides a unique opportunity to investigate neural adaptations underlying successful psychotherapeutic change. Eighteen distressed couples received an average of 23 sessions of EFT, and the resulting functional and structural differences in the neural processing of threat were investigated before and after therapy using MRI methods. Female participants engaged in a stressful task in which they were confronted with the threat of electric shock, while they held their partner’s hand, a stranger’s hand, or were alone in the scanner. Results offered preliminary evidence that EFT can significantly impact emotional dysregulation, promote attenuation of neural threat by their partner, and result in structural change in a key region of emotion circuitry. Moreover, physiological data demonstrated that following EFT for couples, female partners were effectively soothed by their male partners, as demonstrated by decreased cortisol levels.

There is increasing acknowledgement that problematic interpersonal relationships and negative emotions are key factors in the development and maintenance of various forms of psychopathology. Emotionally Focused Therapy (EFT) for couples centers on changing attachment behaviours as a means to improve distressed relationships by helping partners access underlying emotions and foster positive interactions that promote accessibility and trust. EFT is a highly effective therapeutic approach that encourages the development of adaptive emotion regulation observed in secure attachment. The development and emergence of non-invasive neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), provides a unique opportunity to investigate neural adaptations underlying successful psychotherapeutic change. Eighteen distressed couples received an average of 23 sessions of EFT, and the resulting functional and structural differences in the neural processing of threat were investigated before and after therapy using MRI methods. Female participants engaged in a stressful task in which they were confronted with the threat of electric shock, while they held their partner’s hand, a stranger’s hand, or were alone in the scanner. Results offered preliminary evidence that EFT can significantly impact emotional dysregulation, promote attenuation of neural threat by their partner, and result in structural change in a key region of emotion circuitry. Moreover, physiological data demonstrated that following EFT for couples, female partners were effectively soothed by their male partners, as demonstrated by decreased cortisol levels.

Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Recently, many studies have used T1 and T2 quantitative MRI in examining the brain and other body structures, to evaluate and follow up diseases, or simply for better understanding of the human body. Quality control on MRI scanners has been performed since the early eighties and nowadays the ACR MRI phantom is being used for the accreditation of the scanners, and quality control of their qualitative performance. In this study the same phantom is being used to obtain quantitative values of three regions in the phantom that might be used as reference for quantitative quality control. The results of the scans provided quantitative values that can be used as reference for the quality control of qMRI, and there was no difference after scanning the same regions twice. Further study is recommended to provide quantitative values for different MRI scanners strength to assure the use of ACR phantom as a tool for quality control of qMRI scanners. / 2031-01-02

There is increasing acknowledgement that problematic interpersonal relationships and negative emotions are key factors in the development and maintenance of various forms of psychopathology. Emotionally Focused Therapy (EFT) for couples centers on changing attachment behaviours as a means to improve distressed relationships by helping partners access underlying emotions and foster positive interactions that promote accessibility and trust. EFT is a highly effective therapeutic approach that encourages the development of adaptive emotion regulation observed in secure attachment. The development and emergence of non-invasive neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), provides a unique opportunity to investigate neural adaptations underlying successful psychotherapeutic change. Eighteen distressed couples received an average of 23 sessions of EFT, and the resulting functional and structural differences in the neural processing of threat were investigated before and after therapy using MRI methods. Female participants engaged in a stressful task in which they were confronted with the threat of electric shock, while they held their partner’s hand, a stranger’s hand, or were alone in the scanner. Results offered preliminary evidence that EFT can significantly impact emotional dysregulation, promote attenuation of neural threat by their partner, and result in structural change in a key region of emotion circuitry. Moreover, physiological data demonstrated that following EFT for couples, female partners were effectively soothed by their male partners, as demonstrated by decreased cortisol levels.

Den mest etablerade metoden för hjärtavbildning med MRI kallas bSSFP. Denna baseras på att signalen hålls i ett jämviktstillstånd genom noggrann balansering av magnetiska gradientfält. Vid avbildning av objekt i rörelse med hög temporal upplösning sker snabba skiftningar av gradienterna som inducerar virvelströmmar i magnetkamerans ledande komponenter och i patienten. Virvelströmmarna som skapas stör det homogena statiska fältet som krävs för avbildning med bSSFP och leder till artefakter vid avbildning. Det finns därför ett intresse i att kompensera för virvelströmmarnas påverkan vid avbildning. I detta arbete utvärderas tre befintliga kompensationsmetoder: ”Tiny Golden Angle”, ”Double Averaging” och ”Through Slice Equlibriation”. Respektive metod tillåter olika parameterval. Målet med detta arbete är att avgöra vilken, eller vilka, kombinationer av metoderna som ger bäst kompensation för virvelströmmar utan att påverka bildernas kliniska värde. Undersökningen baserades på att kombinera olika metoder samt parametervärden hos respektive metod och applicera detta vid avbildning av ett fantom. Sedan gjordes en kvantitativ analys av fantombilderna och baserat på fantomstudien skedde ett urval av kombinationer för hjärtavbildning av en frivillig testperson. En visuell bedömning gjordes sedan på hjärtbilderna. Resultatet tydde på att individuell applicering av metoderna kompenserade för virvelströmmar, men även att vissa kombinationer av dessa bidrog med förbättrad bildkvalitet. Samtliga bilder bedömdes vara av klinisk kvalitet och resultatet av detta arbete öppnar möjligheten för en klinisk valideringsstudie.

In Dynamic Contrast Enhanced MRI there are several steps from the initial signal to obtaining the pharmacokinetic parameters for tumor characterization. The aim of this work was to validate the steps in the flow of data focusing on T1-mapping, Contrast Agent (CA)-quantification and the pharmacokinetical (PK) model, using a digital phantom of a head. In the Digital Phantom tissues are assigned necessary values to obtain both a regular and contrast enhanced (using Parker AIF) representation and simulating an SPGR signal. The data analysis was performed in a software called MICE, as well as the Digital Phantom developed at the department of Radiation Sciences at Umeå University. The method of variable flip angles for the T1-mapping was analyzed with respect to SNR and number of flip angles, finding that the median value in each tissue is correct and stable. A "two point" inversion recovery sequence was tested with optimal combination of inversion times for white matter and CSF and obtaining correct T1-values when the inversion times were close to the tissue T1, otherwise with large deviations seen. Three different methods for CA-quantification were analyzed and a large underestimation was found assuming a linearity between signal and CA-concentration mainly for vessels at about 60%, but also for other tissue such as white matter at about 15%, improving when the assumption was removed. Still there was a noticeable underestimation of 30% and 10% and the quantification was improved further, achieving a near perfect agreement with the reference concentration, taking the T2*-effect into account. Applying Kety-model, discarding the vp-term, Ktrans was found to be stable with respect to noise in the tumor rim but ve noticeably underestimated with about 50%. The effect of different bolus arrival time, shifting the AIF required in the PK-model with respect to the CA-concentration, was tested with values up to 5 s, obtaining up to about 5% difference in Ktrans as well as the effect of a vascular transport function obtained by the means of an effective mean transit time up to 5 s and up to about 5% difference in Ktrans.

This project focused on the pulmonary application of magnetic resonance (MR) quantitative equilibrium signal (qS0) mapping, dynamic oxygen-enhanced (OE-) magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE-) MRI in asthma and chronic obstructive pulmonary disease (COPD). Initially, a retrospective analysis of MRI and X-ray computed tomography (CT) data from 24 COPD patients and 12 healthy controls demonstrated that MR qS0 mapping had good one-week reproducibility and was comparable to CT in the localization and quantification of emphysema in patients with COPD. In the same data, a reduced oxygen (O2) delivery signal was detected by dynamic OE-MRI in COPD patients regardless of the presence or absence of emphysema on CT, while a significantly reduced baseline spin-lattice relaxation time (T1air) was only observed in emphysematous COPD. Emphysematous COPD also showed significant correlations between dynamic OE-MRI readouts, i.e. enhancing fraction (EF) and the change in the partial pressure of O2 in lung parenchyma (ΔPO2max), and pulmonary diffusion capacity and CT estimates of emphysema. A prospective pilot study was conducted in 10 asthmatic patients which demonstrated that dynamic OE-MRI readouts, including EF, ΔPO2max and O2 wash-in time constant (τup), were reproducible within one month, sensitive to asthma severity and strongly correlated with spirometric readouts of airway function and lung volume. This was followed by a second prospective intervention study in 30 asthmatic patients and 10 healthy controls which revealed a pattern of decreased O2 delivery signal as a response to salbutamol inhalation in severe asthmatics but not in mild asthmatics or healthy controls using short-term repeated dynamic OE-MRI. In addition, DCE-MRI was also performed on 30 asthmatic patients and 10 healthy subjects. A semi-quantitative analysis demonstrated that contrast agent kinetics in asthmatic lungs were characterised by a reduced first-pass peak (SI%max) and a shallower downslope during the late redistribution phase (kwashout) than was observed in healthy controls, and that these were related to pulmonary function test measurements. An extended Tofts model-based quantitative analysis further revealed a significantly increased fractional extravascular extracellular space (ve) in patients with asthma than in healthy controls while the contrast agent transfer coefficient (Ktrans), an index related to vascular permeability, and the fractional blood plasma volume (vp), did not distinguish asthmatics from controls. In conclusion, this project demonstrated the promise of 1) MR qS0 mapping for the assessment of emphysema in COPD lungs, 2) dynamic OE-MRI for the assessment of impaired pulmonary oxygenation in COPD and asthma and for the monitoring of short-term treatment effects in asthma and 3) DCE-MRI for the evaluation of pulmonary microvascular inflammation in asthma. The non-invasive non-ionizing properties and simple setup requirements make these three proton MRI techniques attractive options in the assessment of structural and functional alterations of the lungs in asthma and COPD in clinical settings.

Magnetic resonance imaging is a major advancement in the diagnostic imaging field. Most patients can tolerate an MRI however, there are some who are unable to complete a lengthy scan while lying completely still without sedatives or anesthesia. Non-MRI healthcare providers are trained to use equipment that is “unsafe” in the MRI suite due to the strong magnetic field. Staff who are not fully knowledgeable and trained in MRI safety measures can endanger staff and patients. The purpose of this study was to determine the knowledge level of non-MRI healthcare providers regarding safety risks associated with MRI and to determine their level of satisfaction regarding the MRI safety training they received. This study concluded that non-MRI healthcare providers are knowledgeable about most of the safety hazards. They are satisfied with annual training but would like more in-depth material added to their current learning modules.

The purpose of this thesis was to implement and quantitatively test a quantitative MRI (qMRI) method, from which synthetic MR images are created and also evaluated. The parameter maps of T1, T2*, and effective proton density (PD*) were tested with reference tubes containing different relaxation times, and concentrations of water (H2O) and heavy water (D2O). Two normal volunteers were also used to test qMRI method, by performing regional analysis on the parameter maps of the volunteers. The synthetic FLASH MR images were evaluated by: using the relative standard deviation of a region of interest (ROI) as a measure for the signal-to-noise ratio (SNR), implanting artificial multiple sclerosis (MS) lesions in the parameter maps used to create the synthetic images, and an MRI radiologist opinion of the images. All MRI measurements were conducted on a 3.0 Tesla scanner (Siemens MAGNETOM Skyrafit). The results from reference tube testing, shows that the implementation was reasonably successful, although the T2* maps can not display values on voxels which have T2 exceeding 100 ms. In vivo parameter map ROI values were consistent between volunteers. The SNR and contrast-to-noise ratio of synthetic images are comparable to their measured counterparts depending on TE. The artificial MS lesions were distinguishable from normal appearing tissue in a T1-weighted synthetic FLASH. The radiologist thought the a synthetic T2*-weighted FLASH was somewhat promising for clinical use after further research and development, however a synthetic T1-weighted FLASH had clinical value. / Syftet med detta arbete var att implementera och kvantitativt undersöka en kvantitativ MR (qMRI) metod, för att sedan skapa och utvärdera syntetiska MR-bilder. qMRI-metodens parameterkartor (T1, T2* och effektiv proton densitets PD*) undersöktes med olika typer av referensprover. Dessa prover innehöll skilda relaxationstider, samt olika koncentrationer av vatten (H2O) och tungt vatten (D2O). In vivo parameterkartor från frivilliga granskades genom att jämföra T1, T2* och PD* värdena på intresseområden (ROIs) mellan frivilliga och publicerade värden. Syntetiska FLASH MR-bilder utvärderades genom att: använda relativa standardavvikelsen av ett intresseområde (ROI) som ett mått på signal-brusförhållande (SNR), implantera artificiell multipel skleros (MS) lesioner i de frivilligas parameterkartor för att se ifall dessa kan identifieras i de syntetiska MR-bilder, och slutligen utvärderade en MR-radiolog bilderna. MR-mätningarna utfördes på 3.0 Tesla MR-kamera (Siemens MAGNETOM Skyrafit). Resultaten från referensproverna visar att implementeringen var rimligen framgångsrik, även om beräknade T2* för voxlar som har T2 över 100 ms inte är pålitliga. Frivilligas parameterkartor visade på bra överensstämmelse, dessvärre inte med publicerade. SNR och kontrast-till-brus-förhållandet (CNR) för syntetiska bilder är jämförbara med deras uppmätta motsvarigheter, beroende på TE. De artificiella MS-lesionerna kunde tydligt skiljas från normal omgivande vävnad i en T1-viktad syntetisk FLASH. Radiologen tyckte att en syntetisk T2*-viktad FLASH var något lovande för klinisk användning efter ytterligare förbättringar, medan en syntetisk T1-viktad FLASH hade kliniskt värde.