From 7e12f2ea8616dbcff8f79c5acfab1cbbf7ee9c85 Mon Sep 17 00:00:00 2001 From: Mathieu Boudreau Date: Wed, 9 Oct 2024 09:41:25 -0300 Subject: [PATCH] Add remaining citations --- .../01-Introduction.md | 4 +- .../02-Theory.md | 22 +- .../03-Simulations.md | 4 +- .../A1-Appendix A.md | 2 +- .../A2-Appendix B.md | 8 +- bibliography/mtrchapter.bib | 39 ++ bibliography/mtsatchapter.bib | 540 ++++++++++++++++++ myst.yml | 2 + 8 files changed, 601 insertions(+), 20 deletions(-) create mode 100644 bibliography/mtsatchapter.bib diff --git a/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/01-Introduction.md b/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/01-Introduction.md index ebc17b1..e3a4b35 100644 --- a/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/01-Introduction.md +++ b/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/01-Introduction.md @@ -22,7 +22,7 @@ This content of this section is still a work-in-progress and has not been proofr Magnetization Transfer Saturation (MTsat) is a semi-quantitative MRI technique that offers unique insights into tissue microstructure. Built upon the spoiled gradient-recalled echo (SPGR) sequence, the MTsat protocol acquires images with and without an MT-preparation off-resonance pulse to acquire different contrast that varies with macromolecular density and _T_{sub}`1`. -The foundation of MTsat lies in a 2008 model by Helms and colleagues (Helms et al. 2008), which treats the off-resonance pulse as a second excitation pulse, allowing us to model the effects of MT analytically without the need of the complex Bloch-McConnel equations. Following some reasonable approximations and the acquisition of three distinct MRI images, this model allows for analytical computation of a parameter that models the % reduction in free-pool longitudinal magnetization due to a single off-resonance pulse, MTsat. +The foundation of MTsat lies in a 2008 model by Helms and colleagues [@Helms2008-wf], which treats the off-resonance pulse as a second excitation pulse, allowing us to model the effects of MT analytically without the need of the complex Bloch-McConnel equations. Following some reasonable approximations and the acquisition of three distinct MRI images, this model allows for analytical computation of a parameter that models the % reduction in free-pool longitudinal magnetization due to a single off-resonance pulse, MTsat. This introduction provides a glimpse into the theoretical basis of MTsat, its practical applications, and sensitivity to variables like tissue _T_{sub}`1` and _B_{sub}`1`. By exploring the unique properties and potential of MTsat, we hope to give readers a better understanding of the advantages and limitations of this MRI technique in both research and clinical practice, as well as give a deeper conceptual understanding of what the MTsat value means. @@ -32,7 +32,7 @@ This introduction provides a glimpse into the theoretical basis of MTsat, its pr Simplified pulse sequence diagram of an MTR imaging sequence. An off-resonance and high powered MT-preparation pulse is followed by a spoiler gradient to destroy any transverse magnetization prior the application of the imaging sequence, in this case a spoiled gradient recalled echo (SPGR). ``` -In the initial MTsat paper (Helms et al. 2008, 2010), the main innovation stems from a new model of the MT-weighted SPGR sequence shown in [](#mtsatFig1). There, (Helms et al. 2008) proposed to interpret the effects of the MT-preparation pulse as a second excitation RF pulse of an unknown flip angle. That is to say, they modeled the reduction of the longitudinal magnetization of the free pool due to the MT pulse to be the same reduction caused by the flip angle rotation of a second instantaneous excitation RF pulse. [](#mtsatFig2) presents the Helms model, where to be consistent with the convention presented in mathematical derivations in (Helms et al. 2008, 2010), the order of the pulses are switched such that the readout excitation pulse comes first ({math}`\alpha_{1}`), and the excitation pulse modelling the effects of the MT pulse comes second ({math}`\alpha_{2}`). Note that, after a steady-state is reached, this order would not not impact the signal value during image readout. +In the initial MTsat paper [@Helms2008-wf;@Helms2010-kv], the main innovation stems from a new model of the MT-weighted SPGR sequence shown in [](#mtsatFig1). There, [@Helms2008-wf] proposed to interpret the effects of the MT-preparation pulse as a second excitation RF pulse of an unknown flip angle. That is to say, they modeled the reduction of the longitudinal magnetization of the free pool due to the MT pulse to be the same reduction caused by the flip angle rotation of a second instantaneous excitation RF pulse. [](#mtsatFig2) presents the Helms model, where to be consistent with the convention presented in mathematical derivations in [@Helms2008-wf;@Helms2010-kv], the order of the pulses are switched such that the readout excitation pulse comes first ({math}`\alpha_{1}`), and the excitation pulse modelling the effects of the MT pulse comes second ({math}`\alpha_{2}`). Note that, after a steady-state is reached, this order would not not impact the signal value during image readout. ```{figure} img/mtsat_model_sequence.png :label: mtsatFig2 diff --git a/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/02-Theory.md b/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/02-Theory.md index 01145bb..b095f26 100644 --- a/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/02-Theory.md +++ b/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/02-Theory.md @@ -18,7 +18,7 @@ numbering: This content of this section is still a work-in-progress and has not been proofread and/or reviewed. ::: -MTsat, like MTR and many flavours of quantitative MT, is based on spoiled gradient recalled echo (SPGR) images (Haase et al. 1986; Sekihara 1987; Hargreaves 2012) preceded by an off-resonance RF pulse to provide magnetization transfer contrast (Wolff and Balaban 1989; Henkelman et al. 1993; J. G. Sled and Pike 2000; John G. Sled 2018). [](#mtsatFig1) presents a simplified diagram of this MT-prepared SPGR pulse sequence (imaging gradients are not shown). A standard SPGR sequence (low flip angle [~5-10°], short TR [~10-30ms], and a strong spoiler gradient) are preceded by a long (~10 ms) off-resonance (~1-5 kHz) pulse with a strong peak amplitude (the total pulse has an equivalent on-resonance flip angle of 200°-700°). A smooth shape (e.g. Gaussian or Fermi) is typically used for the off-resonance pulse in order to have a single off-resonance frequency (from Fourier analysis). A strong spoiler gradient is also added between the off-resonance MT-preparation pulse and the on-resonance excitation pulse in order to destroy residual transverse magnetization that may have been created by the off-resonance pulse. Images acquired without MT saturation are acquired using the same timing as this sequence, but with the off-resonance RF pulse either completely off or using a very large off-resonance frequency (e.g. ~30+ kHz). +MTsat, like MTR and many flavours of quantitative MT, is based on spoiled gradient recalled echo (SPGR) images [@Haase1986-kt;@Sekihara1987-bs;@Hargreaves2012-kj] preceded by an off-resonance RF pulse to provide magnetization transfer contrast [@Wolff1989-ag;@Henkelman1993-lt;@Sled2000-pc;@Sled2018-zr]. [](#mtsatFig1) presents a simplified diagram of this MT-prepared SPGR pulse sequence (imaging gradients are not shown). A standard SPGR sequence (low flip angle [~5-10°], short TR [~10-30ms], and a strong spoiler gradient) are preceded by a long (~10 ms) off-resonance (~1-5 kHz) pulse with a strong peak amplitude (the total pulse has an equivalent on-resonance flip angle of 200°-700°). A smooth shape (e.g. Gaussian or Fermi) is typically used for the off-resonance pulse in order to have a single off-resonance frequency (from Fourier analysis). A strong spoiler gradient is also added between the off-resonance MT-preparation pulse and the on-resonance excitation pulse in order to destroy residual transverse magnetization that may have been created by the off-resonance pulse. Images acquired without MT saturation are acquired using the same timing as this sequence, but with the off-resonance RF pulse either completely off or using a very large off-resonance frequency (e.g. ~30+ kHz). ```{math} :label: mtsatEq1 @@ -28,7 +28,7 @@ S\left( \alpha,\text{TR} \right)=A\text{sin}\left( \alpha \right)\frac{1-\text{e \end{equation} ``` -where A is some proportionality constant (e.g. gyromagnetic ratio, density, coil sensitivity, etc), ɑ is the excitation flip angle, _R_{sub}`1` = 1/_T_{sub}`1` (assuming a monoexponential longitudinal relaxation curve), and TR is the repetition time. Similarly, an analytical equation for the steady-state signal of a dual-excitation SPGR experiment ([](#mtsatFig2)) can be derived, and (Helms et al. 2008) demonstrated it to be: +where A is some proportionality constant (e.g. gyromagnetic ratio, density, coil sensitivity, etc), ɑ is the excitation flip angle, _R_{sub}`1` = 1/_T_{sub}`1` (assuming a monoexponential longitudinal relaxation curve), and TR is the repetition time. Similarly, an analytical equation for the steady-state signal of a dual-excitation SPGR experiment ([](#mtsatFig2)) can be derived, and [@Helms2008-wf] demonstrated it to be: ```{math} :label: mtsatEq2 @@ -40,7 +40,7 @@ S\left( \alpha_{1},\text{TR}_{1},\alpha_{2},\text{TR}_{2} \right)=A\text{sin}\le where {math}`\alpha_{1}` is the imaging excitation flip angle, {math}`\alpha_{2}` is the excitation flip angle representing the MT saturation pulse, TR{sub}`1` is the time between {math}`\alpha_{1}` to {math}`\alpha_{2}`, TR{sub}`2` is the time between {math}`\alpha_{2}` and the following {math}`\alpha_{1}`, and TR = TR{sub}`1` + TR{sub}`2`. - [](#mtsatEq2) has three unknowns: _A_, _R_{sub}`1`, and {math}`\alpha_{2}`. Of these three, {math}`\alpha_{2}` is expected to be the most sensitive to macromolecular density via the MT effect, and as such is the parameter that we’d like to calculate or fit using this dual-excitation SPGR model for the MT-prepared SPGR pulse sequence. Although there would be some ways to acquire additional measurements (three unknowns, so at a minimum three measurements are needed) and apply a nonlinear fit to [](#mtsatEq2) to extract {math}`\alpha_{2}`, this method has a long numerical processing time. To shorten the calculation of the parameter maps, (Helms et al. 2008, 2010) proposed some reasonable assumptions that can be made to simplify [](#mtsatEq2). The first proposed assumption is that _R_{sub}`1`*TR << 1, which is true when using typical MT-weighted SPGR protocol parameters (TR ~ 0.01-0.05 s) and in the brain at clinical field strengths (_T_{sub}`1` ~ 1 s, thus _R_{sub}`1` ~ 1 s{sup}`-1`). The same approximation applies to TR{sub}`1` and TR{sub}`2`, which are shorter than TR. This leads to the removal of all exponential functions in [](#mtsatEq2), as via the Taylor expansion of the exponential function, exp(x) ~ 1 + x when abs(x) << 1, and the removal of another term via R{sub}`1`TR{sub}`1` * R{sub}`1`TR{sub}`2` ~ 0 when R{sub}`1`TR{sub}`1` and R{sub}`1`TR{sub}`2` are both << 1. The simplifications result in + [](#mtsatEq2) has three unknowns: _A_, _R_{sub}`1`, and {math}`\alpha_{2}`. Of these three, {math}`\alpha_{2}` is expected to be the most sensitive to macromolecular density via the MT effect, and as such is the parameter that we’d like to calculate or fit using this dual-excitation SPGR model for the MT-prepared SPGR pulse sequence. Although there would be some ways to acquire additional measurements (three unknowns, so at a minimum three measurements are needed) and apply a nonlinear fit to [](#mtsatEq2) to extract {math}`\alpha_{2}`, this method has a long numerical processing time. To shorten the calculation of the parameter maps, [@Helms2008-wf;@Helms2010-kv] (Helms et al. 2008, 2010) proposed some reasonable assumptions that can be made to simplify [](#mtsatEq2). The first proposed assumption is that _R_{sub}`1`TR << 1, which is true when using typical MT-weighted SPGR protocol parameters (TR ~ 0.01-0.05 s) and in the brain at clinical field strengths (_T_{sub}`1` ~ 1 s, thus _R_{sub}`1` ~ 1 s{sup}`-1`). The same approximation applies to TR{sub}`1` and TR{sub}`2`, which are shorter than TR. This leads to the removal of all exponential functions in [](#mtsatEq2), as via the Taylor expansion of the exponential function, exp(x) ~ 1 + x when abs(x) << 1, and the removal of another term via R{sub}`1`TR{sub}`1`R{sub}`1`TR{sub}`2` ~ 0 when R{sub}`1`TR{sub}`1` and R{sub}`1`TR{sub}`2` are both << 1. The simplifications result in ```{math} :label: mtsatEq3 @@ -50,7 +50,7 @@ S\left( \alpha_{1},\text{TR}_{1},\alpha_{2},\text{TR}_{2} \right)=A\text{sin}\le \end{equation} ``` -The second approximation is that {math}`\alpha_{2}` is small (less than 30 degrees), which is to say that the MT saturation is relatively small. This is expected to be true for the tissue properties of the brain (mostly, myelin), but care must be taken with the planned MT pulse parameters as the MT saturation increases with smaller offset frequency and high peak pulse amplitude. Later, we’ll calculate if this is a reasonable assumption for the calculated {math}`\alpha_{2}`. This assumption is integrated into [](#mtsatEq2) via the Taylor series expansion of the {math}`\text{cos} \left( \alpha_{2} \right)`, where {math}`\text{cos} \left( x \right) \approx 1-x^{2}/2`for small x (this relationship is true for x < 30 degrees or 0.5 radians). Introducing this approximation in [3] and with the additional simplifications {math}`\alpha_{2}^{2}` * R{sub}`1`TR ~ 0 (from the assumptions above), this results in +The second approximation is that {math}`\alpha_{2}` is small (less than 30 degrees), which is to say that the MT saturation is relatively small. This is expected to be true for the tissue properties of the brain (mostly, myelin), but care must be taken with the planned MT pulse parameters as the MT saturation increases with smaller offset frequency and high peak pulse amplitude. Later, we’ll calculate if this is a reasonable assumption for the calculated {math}`\alpha_{2}`. This assumption is integrated into [](#mtsatEq2) via the Taylor series expansion of the {math}`\text{cos} \left( \alpha_{2} \right)`, where {math}`\text{cos} \left( x \right) \approx 1-x^{2}/2`for small x (this relationship is true for x < 30 degrees or 0.5 radians). Introducing this approximation in [3] and with the additional simplifications {math}`\alpha_{2}^{2}`R{sub}`1`TR ~ 0 (from the assumptions above), this results in ```{math} :label: mtsatEq4 @@ -80,7 +80,7 @@ S\left( \alpha_{1},\alpha_{2},\text{TR} \right)=A \alpha _{1}\frac{R_{1}\text{TR \end{equation} ``` -[](#mtsatFig3) demonstrates how {math}`\delta`, which represents MTsat as was defined in (Helms et al. 2008), is the fractional reduction in longitudinal magnetization after the MT pulse in the MTsat model illustrated in [](#mtsatFig2) relative to the Mz prior to the pulse. Conventionally, MTsat ({math}`\delta`) is reported in percentage, so {math}`\text{MTsat} = \delta \cdot 100` . +[](#mtsatFig3) demonstrates how {math}`\delta`, which represents MTsat as was defined in [@Helms2008-wf], is the fractional reduction in longitudinal magnetization after the MT pulse in the MTsat model illustrated in [](#mtsatFig2) relative to the Mz prior to the pulse. Conventionally, MTsat ({math}`\delta`) is reported in percentage, so {math}`\text{MTsat} = \delta \cdot 100` . ```{figure} img/mtsat_trig.png :label: mtsatFig3 @@ -88,7 +88,7 @@ S\left( \alpha_{1},\alpha_{2},\text{TR} \right)=A \alpha _{1}\frac{R_{1}\text{TR Demonstration through trigonometry of how following a small flip angle {math}`\alpha_{2}` (eg MT saturation), the value {math}`\delta \equiv \alpha_{2}^{2}/2` represents the fraction of the reduction in longitudinal magnetization due to the pulse (bigDelta) relative to the value prior to the pulse (Mz{sub}`before`). ``` -Before jumping into how to measure MTsat, let's demonstrate some expected properties and values using known values from a simpler MTR experiment. From the MTR protocol in (Brown, Narayanan, and Arnold 2013) of the MTR blog post, 1=15 deg and TR = 0.03 s, so assuming a _T_{sub}`1` at 1.5T (field strength that Brown used) of 0.55 s in healthy WM, so R{sub}`1` = 1.8. First off, [](#mtsatFig3) with no MT pulse (thus {math}`\delta` = 0) should converge close to the well-known SPGR equation [1]. Inputting the values in each equations, we get 0.0816A for [1], and 0.0815A, thus they are in close agreement. Next, we can get an estimated value of MTsat, using a known MTR value, the calculated S0 value (which we just did), and then solving [5] for {math}`\delta` using the MTR equation to bring everything together. Doing so is shown in [Appendix A](#mtsatAppendixA), from there and using our simulations in the MTR post with Brown2013 for healthier WM (MTR = 46%), we get an MTsat value of 4.92% ({math}`\delta` = 0.0492), which is close to some reported MTsat values in the literature (Karakuzu et al. 2022). From there, and by definition of {math}`\delta`, the modeled {math}`\alpha_{2}` in [](#mtsatFig2) for this example is 18 degrees, confirming that earlier assumption that {math}`\alpha_{2}` < 30 degrees for that approximation. +Before jumping into how to measure MTsat, let's demonstrate some expected properties and values using known values from a simpler MTR experiment. From the MTR protocol in [@Brown2013-eg] of the MTR section, {math}`\alpha_{1}`=15 deg and TR = 0.03 s, so assuming a _T_{sub}`1` at 1.5T (field strength that Brown used) of 0.55 s in healthy WM, so R{sub}`1` = 1.8. First off, [](#mtsatFig3) with no MT pulse (thus {math}`\delta` = 0) should converge close to the well-known SPGR equation [1]. Inputting the values in each equations, we get 0.0816A for [1], and 0.0815A, thus they are in close agreement. Next, we can get an estimated value of MTsat, using a known MTR value, the calculated S0 value (which we just did), and then solving [5] for {math}`\delta` using the MTR equation to bring everything together. Doing so is shown in [Appendix A](#mtsatAppendixA), from there and using our simulations in the MTR post with [@Brown2013-eg] for healthier WM (MTR = 46%), we get an MTsat value of 4.92% ({math}`\delta` = 0.0492), which is close to some reported MTsat values in the literature (Karakuzu et al. 2022). From there, and by definition of {math}`\delta`, the modeled {math}`\alpha_{2}` in [](#mtsatFig2) for this example is 18 degrees, confirming that earlier assumption that {math}`\alpha_{2}` < 30 degrees for that approximation. In that example, we used a known _T_{sub}`1` value to extract MTsat using a two-measurement MTR experiment, but in practice this value is not known and varies per-pixel across tissues. Although we could use an additionally measured _T_{sub}`1` map to do this, this can be time consuming depending on the method used. (Helms et al. 2008, 2010) thus demonstrated that with one additional T1w measurement that uses no MT preparation pulse but has different {math}`\alpha_{1}`/TR than the MTon (MTw) and MToff (PDw) measurements used for MTR, that MTsat can be calculated analytically, and as a bonus a _T_{sub}`1` map is also calculated in the process. (This makes sense, as the VFA _T_{sub}`1` mapping sequence is often just two SPGR measurements with different {math}`\alpha` values). Thus, using this three measurement protocol (MTw/PDw/T1w, which we’ll call the MTsat protocol), MTsat and _T_{sub}`1` (1/R{sub}`1`) can be calculated analytically pixelwise using the following set of equations (derived from [](#mtsatEq5)): @@ -122,11 +122,11 @@ Remember, like MTR, MTsat is calculated from the equations above following the a - - - - - + + + + + diff --git a/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/03-Simulations.md b/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/03-Simulations.md index 02389cd..5ed53ee 100644 --- a/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/03-Simulations.md +++ b/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/03-Simulations.md @@ -20,7 +20,7 @@ This content of this section is still a work-in-progress and has not been proofr In line with our previous MTR blog post, we employ the qMRLab qMT simulations to model MTsat measurements and subsequently calculate MTsat values from [](#mtsatEq7), [](#mtsatEq8), and [](#mtsatEq9). [](#qmtParamsTable2) lists the essential tissue parameters used for the simulations. [](#mtsatPlot1) plots the MTsat values that have been calculated for each protocol outlined in [](#mtsatProtocolTable), while also incorporating the relevant tissue parameters found in [](#qmtParamsTable2). -:::{table} Quantitative MT parameters in healthy and diseased human tissue reported for a study at 1.5 T (Sled 2001). +:::{table} Quantitative MT parameters in healthy and diseased human tissue reported for a study at 1.5 T [@Sled2001-fz]. :label: qmtParamsTable2 :enumerator: 6.5
Helms 2008Weiskopf 2013Campbell 2018Karakuzu 2022York 2022[@Helms2008-wf][@Weiskopf2013-lp][@Campbell2018-hi][@Karakuzu2022-af][@York2022-fl]
@@ -99,7 +99,7 @@ To assess the relationship between MTsat and _T_{sub}`1`, we conducted simulatio MTR/_T_{sub}`1,meas`/MTsat vs _T_{sub}`1` values ::: -Similarly, we can investigate the sensitivity of MTsat to _B_{sub}`1`, which varies substantially in the scanner at magnetic field strengths of 3T and above. In the human brain, _B_{sub}`1` typically fluctuates the nominal flip angles within a range of -30% to 10% (Boudreau et al. 2017). [](#mtsatPlot3) displays the calculated MTR, MTsat, and _T_{sub}`1` values using a range of _B_{sub}`1` values +-30% to both the excitation and MT pulses. All three parameters demonstrate high sensitivity to changes in _B_{sub}`1`. Notably, while _T_{sub}`1` is relatively insensitive to minor magnetic field variations, the calculated _T_{sub}`1` values may deviate from accuracy. In contrast, the calculated MTsat inherently reflects the actual saturation induced by the MT pulse, which is directly proportional to _B_{sub}`1`. This relationship is expected since lower _B_{sub}`1` values result in lower true MTsat values, which is particularly relevant when attempting to use MTsat as a biomarker for myelin content. To address this issue, an empirical equation (Weiskopf et al. 2013) has been introduced to estimate the MTsat value that would have been measured if _B_{sub}`1` values had been uniform across the brain, although it's essential to emphasize that this is not a representation of the actual MTsat values the tissue experiences, but a means to standardize MTsat even in the presence of inhomogeneous _B_{sub}`1` maps if/when RF transmit shimming isn’t done. +Similarly, we can investigate the sensitivity of MTsat to _B_{sub}`1`, which varies substantially in the scanner at magnetic field strengths of 3T and above. In the human brain, _B_{sub}`1` typically fluctuates the nominal flip angles within a range of -30% to 10% (Boudreau et al. 2017). [](#mtsatPlot3) displays the calculated MTR, MTsat, and _T_{sub}`1` values using a range of _B_{sub}`1` values +-30% to both the excitation and MT pulses. All three parameters demonstrate high sensitivity to changes in _B_{sub}`1`. Notably, while _T_{sub}`1` is relatively insensitive to minor magnetic field variations, the calculated _T_{sub}`1` values may deviate from accuracy. In contrast, the calculated MTsat inherently reflects the actual saturation induced by the MT pulse, which is directly proportional to _B_{sub}`1`. This relationship is expected since lower _B_{sub}`1` values result in lower true MTsat values, which is particularly relevant when attempting to use MTsat as a biomarker for myelin content. To address this issue, an empirical equation [@Weiskopf2013-lp] has been introduced to estimate the MTsat value that would have been measured if _B_{sub}`1` values had been uniform across the brain, although it's essential to emphasize that this is not a representation of the actual MTsat values the tissue experiences, but a means to standardize MTsat even in the presence of inhomogeneous _B_{sub}`1` maps if/when RF transmit shimming isn’t done. :::{figure} #mtsatFig3cell :label: mtsatPlot3 diff --git a/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/A1-Appendix A.md b/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/A1-Appendix A.md index a878368..650fb7a 100644 --- a/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/A1-Appendix A.md +++ b/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/A1-Appendix A.md @@ -21,7 +21,7 @@ This content of this section is still a work-in-progress and has not been proofr ## Derivation -From the MTR protocol in Brown 2013 of the MTR blog post, 1=15 deg and TR = 0.03 s, so assuming a _T_{sub}`1` at 1.5T (field strength that Brown used) of 0.55 s in healthy WM, so _R_{sub}`1` = 1.8, we can calculate the signal from [5] of an experiment with no MT pulse ({math}`\alpha_{2}` = 0). +From the MTR protocol in [Brown2013-eg] of the MTR section, {math}`\alpha_{1}`=15 deg and TR = 0.03 s, so assuming a _T_{sub}`1` at 1.5T (field strength that Brown used) of 0.55 s in healthy WM, so _R_{sub}`1` = 1.8, we can calculate the signal from [#mtsatEq6] of an experiment with no MT pulse ({math}`\alpha_{2}` = 0). diff --git a/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/A2-Appendix B.md b/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/A2-Appendix B.md index d49fb6f..c43cbcd 100644 --- a/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/A2-Appendix B.md +++ b/6 Magnetization Transfer Imaging/3 Magnetization Transfer Saturation/A2-Appendix B.md @@ -19,7 +19,7 @@ numbering: This content of this section is still a work-in-progress and has not been proofread and/or reviewed. ::: -So far we’ve explored a lot of the practical properties of MTsat, but have yet to explore what this parameter represents in reality. We begin this discussion by looking at how (Helms et al. 2008) interpreted MTsat: +So far we’ve explored a lot of the practical properties of MTsat, but have yet to explore what this parameter represents in reality. We begin this discussion by looking at how [@Helms2008-wf] interpreted MTsat: (figure or quote) @@ -39,7 +39,7 @@ Demonstration through trigonometry of how following a small flip angle alpha2 (e ## Simulation 1: Revisiting MTsat Theory -In our first simulation, we use the qMRLab qMT-SPGR module to simulate steady-state signals from an MTsat experiment on healthy white matter tissues. We utilize tissue parameters from Sled (2011) and an MTsat protocol derived from Karakuzu (2022). +In our first simulation, we use the qMRLab qMT-SPGR module to simulate steady-state signals from an MTsat experiment on healthy white matter tissues. We utilize tissue parameters from [@Sled2001-fz] and an MTsat protocol derived from [@Karakuzu2022-af]. :::{dropdown} Code @@ -203,7 +203,7 @@ T1s = ::: -Our results closely align with expectations (_T_{sub}`1` fitted ~= _T_{sub}`1` input, MTR ~58, MTsat ~5%). Converting the MTsat value to ɑ2 (see Figure 8), we find that the MTSat value corresponds to an equivalent excitation pulse of approximately 18.7 degrees. Through Helms' interpretation, we infer that the MT pulse should be reducing the longitudinal magnetization by roughly 0.05 (ie Mz_after pulse - Mz_before pulse = 0.05). +Our results closely align with expectations (_T_{sub}`1` fitted ~= _T_{sub}`1` input, MTR ~58, MTsat ~5%). Converting the MTsat value to ɑ2 (see [#mtsatFig3]), we find that the MTSat value corresponds to an equivalent excitation pulse of approximately 18.7 degrees. Through Helms' interpretation, we infer that the MT pulse should be reducing the longitudinal magnetization by roughly 0.05 (ie Mz_after pulse - Mz_before pulse = 0.05). ## Simulation 2: Challenging MTSat Model Assumptions @@ -253,7 +253,7 @@ legend('1-Mz_{after}/Mz_{before}') :label: mtsatAppendixPlotB1 ::: -From these simulations, we find that there is a 0.314% reduction in longitudinal magnetization before/after the MT pulse after a steady state is achieved, which is an order of magnitude smaller than the MTsat value we calculated earlier for this protocol and tissue parameters (~5%). Either the MTsat theory is wrong, or we’re missing something. Revisiting the pulse sequence (Figure 1) and the MTsat model (Figure 2), we notice that while the MTsat model assumes instant excitation for both pulses, in reality the MT pulse is relatively long (~10 ms, Table 1). So, while there is a decoupling between MT saturation and relaxation in the MTsat model (Figure 2), in reality (and in our simulations) there is relaxation occurring during the MT pulse, and we didn’t account for that in the above simulation. +From these simulations, we find that there is a 0.314% reduction in longitudinal magnetization before/after the MT pulse after a steady state is achieved, which is an order of magnitude smaller than the MTsat value we calculated earlier for this protocol and tissue parameters (~5%). Either the MTsat theory is wrong, or we’re missing something. Revisiting the pulse sequence ([#mtsatFig1]) and the MTsat model ([#mtsatFig2]), we notice that while the MTsat model assumes instant excitation for both pulses, in reality the MT pulse is relatively long (~10 ms, [#mtsatProtocolTable]). So, while there is a decoupling between MT saturation and relaxation in the MTsat model ([#mtsatFig2]), in reality (and in our simulations) there is relaxation occurring during the MT pulse, and we didn’t account for that in the above simulation. ## Simulation 3: _T_{sub}`1` Correction During MT Pulse diff --git a/bibliography/mtrchapter.bib b/bibliography/mtrchapter.bib index 6cc9dde..38e25b8 100644 --- a/bibliography/mtrchapter.bib +++ b/bibliography/mtrchapter.bib @@ -390,3 +390,42 @@ @ARTICLE{Brown2013-eg transfer ratio; Multiple sclerosis; Remyelination", language = "en" } +,@ARTICLE{Karakuzu2022-af, + title = "Vendor-neutral sequences and fully transparent workflows improve + inter-vendor reproducibility of quantitative {MRI}", + author = "Karakuzu, Agah and Biswas, Labonny and Cohen-Adad, Julien and + Stikov, Nikola", + journal = "Magn. Reson. Med.", + volume = 88, + number = 3, + pages = "1212--1228", + abstract = "PURPOSE: We developed an end-to-end workflow that starts with a + vendor-neutral acquisition and tested the hypothesis that + vendor-neutral sequences decrease inter-vendor variability of T1, + magnetization transfer ratio (MTR), and magnetization transfer + saturation-index (MTsat) measurements. METHODS: We developed and + deployed a vendor-neutral 3D spoiled gradient-echo (SPGR) sequence + on three clinical scanners by two MRI vendors. We then acquired T1 + maps on the ISMRM-NIST system phantom, as well as T1, MTR, and + MTsat maps in three healthy participants. We performed + hierarchical shift function analysis in vivo to characterize the + differences between scanners when the vendor-neutral sequence is + used instead of commercial vendor implementations. Inter-vendor + deviations were compared for statistical significance to test the + hypothesis. RESULTS: In the phantom, the vendor-neutral sequence + reduced inter-vendor differences from 8\% to 19.4\% to 0.2\% to + 5\% with an overall accuracy improvement, reducing ground truth T1 + deviations from 7\% to 11\% to 0.2\% to 4\%. In vivo, we found + that the variability between vendors is significantly reduced (p = + 0.015) for all maps (T1, MTR, and MTsat) using the vendor-neutral + sequence. CONCLUSION: We conclude that vendor-neutral workflows + are feasible and compatible with clinical MRI scanners. The + significant reduction of inter-vendor variability using + vendor-neutral sequences has important implications for qMRI + research and for the reliability of multicenter clinical trials.", + month = sep, + year = 2022, + keywords = "magnetization transfer; multicenter; open source; qMRI; + relaxometry; reproducibility; vendor neutral", + language = "en" +} diff --git a/bibliography/mtsatchapter.bib b/bibliography/mtsatchapter.bib new file mode 100644 index 0000000..8183d28 --- /dev/null +++ b/bibliography/mtsatchapter.bib @@ -0,0 +1,540 @@ +@ARTICLE{Wolff1989-ag, + title = "Magnetization transfer contrast ({MTC}) and tissue water proton + relaxation in vivo", + author = "Wolff, S D and Balaban, R S", + journal = "Magn. Reson. Med.", + volume = 10, + number = 1, + pages = "135--144", + abstract = "In this study the exchange between 1H magnetization in ``free'' + water (1Hf) and that in a pool with restricted motion (1Hr) was + observed in tissues in vivo using NMR saturation transfer methods. + Exchange between these two pools was demonstrated by a decrease in + the steady-state magnetization and relaxation times of 1Hf with + radiofrequency irradiation of 1Hr. The pseudo-first-order rate + constant for the movement of magnetization from 1Hf to 1Hr was + approximately 1 s-1 in kidney and approximately 3 s-1 in skeletal + muscle in vivo. Proton NMR imaging demonstrated that this exchange + was tissue specific and generated a novel form of NMR image + contrast. The extent of exchange between 1Hf and 1Hr as well as + the topological correlation of the exchange with relaxation + weighted images suggests that this pathway is a major determinant + of the observed relaxation properties of water 1H in vivo.", + month = apr, + year = 1989, + language = "en" +} +,@ARTICLE{Karakuzu2022-af, + title = "Vendor-neutral sequences and fully transparent workflows improve + inter-vendor reproducibility of quantitative {MRI}", + author = "Karakuzu, Agah and Biswas, Labonny and Cohen-Adad, Julien and + Stikov, Nikola", + journal = "Magn. Reson. Med.", + volume = 88, + number = 3, + pages = "1212--1228", + abstract = "PURPOSE: We developed an end-to-end workflow that starts with a + vendor-neutral acquisition and tested the hypothesis that + vendor-neutral sequences decrease inter-vendor variability of T1, + magnetization transfer ratio (MTR), and magnetization transfer + saturation-index (MTsat) measurements. METHODS: We developed and + deployed a vendor-neutral 3D spoiled gradient-echo (SPGR) sequence + on three clinical scanners by two MRI vendors. We then acquired T1 + maps on the ISMRM-NIST system phantom, as well as T1, MTR, and + MTsat maps in three healthy participants. We performed + hierarchical shift function analysis in vivo to characterize the + differences between scanners when the vendor-neutral sequence is + used instead of commercial vendor implementations. Inter-vendor + deviations were compared for statistical significance to test the + hypothesis. RESULTS: In the phantom, the vendor-neutral sequence + reduced inter-vendor differences from 8\% to 19.4\% to 0.2\% to + 5\% with an overall accuracy improvement, reducing ground truth T1 + deviations from 7\% to 11\% to 0.2\% to 4\%. In vivo, we found + that the variability between vendors is significantly reduced (p = + 0.015) for all maps (T1, MTR, and MTsat) using the vendor-neutral + sequence. CONCLUSION: We conclude that vendor-neutral workflows + are feasible and compatible with clinical MRI scanners. The + significant reduction of inter-vendor variability using + vendor-neutral sequences has important implications for qMRI + research and for the reliability of multicenter clinical trials.", + month = sep, + year = 2022, + keywords = "magnetization transfer; multicenter; open source; qMRI; + relaxometry; reproducibility; vendor neutral", + language = "en" +} +,@ARTICLE{Boudreau2017-ik, + title = "{B1} mapping for bias-correction in quantitative {T1} imaging of + the brain at {3T} using standard pulse sequences", + author = "Boudreau, Mathieu and Tardif, Christine L and Stikov, Nikola and + Sled, John G and Lee, Wayne and Pike, G Bruce", + journal = "J. Magn. Reson. Imaging", + volume = 46, + number = 6, + pages = "1673--1682", + abstract = "PURPOSE: B1 mapping is important for many quantitative imaging + protocols, particularly those that include whole-brain T1 mapping + using the variable flip angle (VFA) technique. However, B1 mapping + sequences are not typically available on many magnetic resonance + imaging (MRI) scanners. The aim of this work was to demonstrate + that B1 mapping implemented using standard scanner product pulse + sequences can produce B1 (and VFA T1 ) maps comparable in quality + and acquisition time to advanced techniques. MATERIALS AND + METHODS: Six healthy subjects were scanned at 3.0T. An interleaved + multislice spin-echo echo planar imaging double-angle (EPI-DA) B1 + mapping protocol, using a standard product pulse sequence, was + compared to two alternative methods (actual flip angle imaging, + AFI, and Bloch-Siegert shift, BS). Single-slice spin-echo DA B1 + maps were used as a reference for comparison (Ref. DA). VFA flip + angles were scaled using each B1 map prior to fitting T1 ; the + nominal flip angle case was also compared. RESULTS: The + pooled-subject voxelwise correlation (ρ) for B1 maps + (BS/AFI/EPI-DA) relative to the reference B1 scan (Ref. DA) were ρ + = 0.92/0.95/0.98. VFA T1 correlations using these maps were ρ = + 0.86/0.88/0.96, much better than without B1 correction (ρ = 0.53). + The relative error for each B1 map (BS/AFI/EPI-DA/Nominal) had + 95th percentiles of 5/4/3/13\%. CONCLUSION: Our findings show that + B1 mapping implemented using product pulse sequences can provide + excellent quality B1 (and VFA T1 ) maps, comparable to other + custom techniques. This fast whole-brain measurement (∼2 min) can + serve as an excellent alternative for researchers without access + to advanced B1 pulse sequences. LEVEL OF EVIDENCE: 1 Technical + Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1673-1682.", + month = dec, + year = 2017, + keywords = "B1 mapping; Bloch-Siegert shift; T1 mapping; actual flip angle + imaging; double angle method; echo planar imaging", + language = "en" +} +,@ARTICLE{Sekihara1987-bs, + title = "Steady-state magnetizations in rapid {NMR} imaging using small + flip angles and short repetition intervals", + author = "Sekihara, K", + journal = "IEEE Trans. Med. Imaging", + volume = 6, + number = 2, + pages = "157--164", + abstract = "The steady-state magnetizations in three versions of rapid NMR + imaging using small flip angles and short repetition intervals are + studied. It is shown that in the original version, the estimation + using (1 - E(1)) sin alpha/(1 - E(1) cos alpha) contains errors + that depend on the increment of the phase rotation angle arising + from the phase encoding process. The modified version of rapid + imaging, where the phase rotation due to the phase encoding + process is compensated for in each time interval, can have + sensitivity superior to the original version where the phase + rotation is not compensated for. Here, flip angles larger than the + Ernst angle must be used. In the third version, the steady-state + magnetization is obtained by a rapid imaging sequence in which the + phase rotations arising not only from the application of the phase + encoding gradient but also from the applications of other + gradients are compensated for. Analysis of this version showed a + remarkable increase in sensitivity although it required the use of + an extremely uniform field. It is estimated that this increase + reaches 80 percent with a repetition interval of 10 ms, although a + field uniformity less than 1 muT is necessary.", + year = 1987, + language = "en" +} +,@ARTICLE{Sled2000-pc, + title = "Quantitative interpretation of magnetization transfer in spoiled + gradient echo {MRI} sequences", + author = "Sled, J G and Pike, G B", + journal = "J. Magn. Reson.", + volume = 145, + number = 1, + pages = "24--36", + abstract = "A method for analyzing general pulsed magnetization transfer (MT) + experiments in which off-resonance saturation pulses are + interleaved with on-resonance excitation pulses is presented. We + apply this method to develop a steady-state signal equation for + MT-weighted spoiled gradient echo sequences and consider + approximations that facilitate its rapid computation. Using this + equation, we assess various experimental designs for + quantitatively imaging the fractional size of the restricted pool, + cross-relaxation rate, and T(1) and T(2) relaxation times of the + two pools in a binary spin bath system. From experiments on agar + gel, this method is shown to reliably and accurately estimate the + exchange and relaxation properties of a material in an imaging + context, suggesting the feasibility of using this technique in + vivo.", + month = jul, + year = 2000, + language = "en" +} +,@ARTICLE{Haase1986-kt, + title = "{FLASH} imaging. Rapid {NMR} imaging using low flip-angle pulses", + author = "Haase, A and Frahm, J and Matthaei, D and Hanicke, W and Merboldt, + K-D", + journal = "J. Magn. Reson.", + volume = 67, + number = 2, + pages = "258--266", + abstract = "A new method for rapid NMR imaging dubbed FLASH (fast low-angle + shot) imaging is described which, for example, allows measuring + times of the order of 1 s (64 × 128 pixel resolution) or 6 s (256 + × 256 pixels). The technique takes advantage of excitation pulses + with small flip angles eliminating the need of waiting periods in + between successive experiments. It is based on the acquisition of + the free induction decay in the form of a gradient echo generated + by reversal of the read gradient. The entire imaging time is only + given by the number of projections desired times the duration of + slice selection and data acquisition. The method results in about + a 100-fold reduction in measuring time without sacrificing spatial + resolution. Further advantages are an optimized signal-to-noise + ratio, the applicability of commercial gradient systems, and the + deposition of extremely low rf power. FLASH imaging is + demonstrated on phantoms, animals, and human extremities using a + 2.3 T 40 cm bore magnet system. 1H NMR images are obtained with + variable relaxation time contrasts and without motional artifacts.", + month = apr, + year = 1986 +} +,@ARTICLE{Weiskopf2013-lp, + title = "Quantitative multi-parameter mapping of {R1}, {PD}(*), {MT}, and + {R2}(*) at {3T}: a multi-center validation", + author = "Weiskopf, Nikolaus and Suckling, John and Williams, Guy and + Correia, Marta M and Inkster, Becky and Tait, Roger and Ooi, Cinly + and Bullmore, Edward T and Lutti, Antoine", + journal = "Front. Neurosci.", + volume = 7, + pages = 95, + abstract = "Multi-center studies using magnetic resonance imaging facilitate + studying small effect sizes, global population variance and rare + diseases. The reliability and sensitivity of these multi-center + studies crucially depend on the comparability of the data + generated at different sites and time points. The level of + inter-site comparability is still controversial for conventional + anatomical T1-weighted MRI data. Quantitative multi-parameter + mapping (MPM) was designed to provide MR parameter measures that + are comparable across sites and time points, i.e., 1 mm + high-resolution maps of the longitudinal relaxation rate (R1 = + 1/T1), effective proton density (PD(*)), magnetization transfer + saturation (MT) and effective transverse relaxation rate (R2(*) = + 1/T2(*)). MPM was validated at 3T for use in multi-center studies + by scanning five volunteers at three different sites. We + determined the inter-site bias, inter-site and intra-site + coefficient of variation (CoV) for typical morphometric measures + [i.e., gray matter (GM) probability maps used in voxel-based + morphometry] and the four quantitative parameters. The inter-site + bias and CoV were smaller than 3.1 and 8\%, respectively, except + for the inter-site CoV of R2(*) (<20\%). The GM probability maps + based on the MT parameter maps had a 14\% higher inter-site + reproducibility than maps based on conventional T1-weighted + images. The low inter-site bias and variance in the parameters and + derived GM probability maps confirm the high comparability of the + quantitative maps across sites and time points. The reliability, + short acquisition time, high resolution and the detailed insights + into the brain microstructure provided by MPM makes it an + efficient tool for multi-center imaging studies.", + month = jun, + year = 2013, + keywords = "3T; MPM; MT; PD; T1; T2*; multi-center; qMRI", + language = "en" +} +,@ARTICLE{Helms2010-kv, + title = "Erratum to: Helms, dathe, kallenberg and dechent, high-resolution + maps of magnetization transfer with inherent correction for rf + inhomogeneity and {T} 1 relaxation obtained from {3D} {FLASH} + {MRI}. Magn Reson Med 2008 Dec;60(6):1396-1407", + author = "{Helms} and {Dathe} and {Kallenberg} and {Dechent}", + journal = "Magn. Reson. Med.", + publisher = "Wiley", + volume = 64, + number = 6, + pages = "1856--1856", + month = dec, + year = 2010, + language = "en" +} +,@ARTICLE{Henkelman1993-lt, + title = "Quantitative interpretation of magnetization transfer", + author = "Henkelman, R M and Huang, X and Xiang, Q S and Stanisz, G J and + Swanson, S D and Bronskill, M J", + journal = "Magn. Reson. Med.", + volume = 29, + number = 6, + pages = "759--766", + abstract = "Magnetization transfer contrast (MTC) experiments using + off-resonance irradiation have been performed with an agar gel + model by systematically varying offset frequency, amplitude of the + RF irradiation and gel concentration. The experimental results are + shown to be quantitatively modelled by a two-pool system + consisting of a liquid pool with a Lorentzian line shape and a + small semisolid pool with a Gaussian lineshape. The fitted model + yields physically realistic fundamental parameters with a T2 of + the semisolid pool of 13 microseconds. Further analysis shows that + the off-resonance irradiation MTC experiment had significant + limitations in its ability to saturate the semisolid pool without + directly affecting the liquid component.", + month = jun, + year = 1993, + language = "en" +} +,@ARTICLE{Hargreaves2012-kj, + title = "Rapid gradient-echo imaging", + author = "Hargreaves, Brian A", + journal = "J. Magn. Reson. Imaging", + volume = 36, + number = 6, + pages = "1300--1313", + abstract = "Gradient-echo sequences are widely used in magnetic resonance + imaging (MRI) for numerous applications ranging from angiography + to perfusion to functional MRI. Compared with spin-echo + techniques, the very short repetition times of gradient-echo + methods enable very rapid 2D and 3D imaging, but also lead to + complicated ``steady states.'' Signal and contrast behavior can be + described graphically and mathematically, and depends strongly on + the type of spoiling: fully balanced (no spoiling), gradient + spoiling, or radiofrequency (RF)-spoiling. These spoiling options + trade off between high signal and pure T(1) contrast, while the + flip angle also affects image contrast in all cases, both of which + can be demonstrated theoretically and in image examples. As with + spin-echo sequences, magnetization preparation can be added to + gradient-echo sequences to alter image contrast. Gradient-echo + sequences are widely used for numerous applications such as 3D + perfusion imaging, functional MRI, cardiac imaging, and MR + angiography.", + month = dec, + year = 2012, + language = "en" +} +,@ARTICLE{Sled2018-zr, + title = "Modelling and interpretation of magnetization transfer imaging in + the brain", + author = "Sled, John G", + journal = "Neuroimage", + volume = 182, + pages = "128--135", + abstract = "Magnetization transfer contrast has yielded insight into brain + tissue microstructure changes across the lifespan and in a range + of disorders. This progress has been aided by the development of + quantitative magnetization transfer imaging techniques able to + extract intrinsic properties of the tissue that are independent of + the specifics of the data acquisition. While the tissue properties + extracted by these techniques do not map directly onto specific + cellular structures or pathological processes, a growing body of + work from animal models and histopathological correlations aids + the in vivo interpretation of magnetization transfer properties of + tissue. This review examines the biophysical models that have been + developed to describe magnetization transfer contrast in tissue as + well as the experimental evidence for the biological + interpretation of magnetization transfer data in health and + disease.", + month = nov, + year = 2018, + keywords = "Chemical exchange saturation transfer; Grey matter; Inhomogeneous + magnetization transfer; Magnetization transfer; Quantitative + magnetic resonance imaging; Tissue microstructure; White matter", + language = "en" +} +,@ARTICLE{Helms2008-wf, + title = "High-resolution maps of magnetization transfer with inherent + correction for {RF} inhomogeneity and {T1} relaxation obtained + from {3D} {FLASH} {MRI}", + author = "Helms, Gunther and Dathe, Henning and Kallenberg, Kai and Dechent, + Peter", + journal = "Magn. Reson. Med.", + volume = 60, + number = 6, + pages = "1396--1407", + abstract = "An empirical equation for the magnetization transfer (MT) FLASH + signal is derived by analogy to dual-excitation FLASH, introducing + a novel semiquantitative parameter for MT, the percentage + saturation imposed by one MT pulse during TR. This parameter is + obtained by a linear transformation of the inverse signal, using + two reference experiments of proton density and T(1) weighting. + The influence of sequence parameters on the MT saturation was + studied. An 8.5-min protocol for brain imaging at 3 T was based on + nonselective sagittal 3D-FLASH at 1.25 mm isotropic resolution + using partial acquisition techniques (TR/TE/alpha = 25ms/4.9ms/5 + degrees or 11ms/4.9ms/15 degrees for the T(1) reference). A 12.8 + ms Gaussian MT pulse was applied 2.2 kHz off-resonance with 540 + degrees flip angle. The MT saturation maps showed an excellent + contrast in the brain due to clearly separated distributions for + white and gray matter and cerebrospinal fluid. Within the limits + of the approximation (excitation <15 degrees , TR/T(1) less sign + 1) the MT term depends mainly on TR, the energy and offset of the + MT pulse, but hardly on excitation and T(1) relaxation. It is + inherently compensated for inhomogeneities of receive and transmit + RF fields. The MT saturation appeared to be a sensitive parameter + to depict MS lesions and alterations of normal-appearing white + matter.", + month = dec, + year = 2008, + language = "en" +} +,@ARTICLE{Brown2013-eg, + title = "Segmentation of magnetization transfer ratio lesions for + longitudinal analysis of demyelination and remyelination in + multiple sclerosis", + author = "Brown, Robert A and Narayanan, Sridar and Arnold, Douglas L", + journal = "Neuroimage", + volume = 66, + pages = "103--109", + abstract = "We demonstrate a new technique to quantify longitudinal changes in + magnetization transfer ratio (MTR) magnetic resonance imaging + (MRI). These changes are indicative of demyelination and + remyelination. This technique comprises a definition of ΔMTR + lesions, which are identified directly from the MTR images, and an + automatic procedure for segmenting these lesions. We used this + technique to analyze MTR changes in lesions of subjects with + rapidly progressing multiple sclerosis before and after treatment + with immunoablation and autologous stem cell transplant. Subjects + who experienced clinical improvement after treatment showed + significantly improved MTR recovery in lesions that were + recovering during treatment (p<0.0001) while those who were + clinically stable after treatment showed significantly poorer MTR + recovery (p=0.002). The statistical power of this technique to + detect treatment effects on MTR recovery was shown to be + considerably better than previous methods. These results suggest + that longitudinal measurements of MTR in ΔMTR lesions may be an + important technique for the assessment of treatment effects on + remyelination in clinical trials.", + month = feb, + year = 2013, + keywords = "Image processing; Magnetic resonance imaging; Magnetization + transfer ratio; Multiple sclerosis; Remyelination", + language = "en" +} +,@ARTICLE{Weiskopf2013-lp, + title = "Quantitative multi-parameter mapping of {R1}, {PD}(*), {MT}, and + {R2}(*) at {3T}: a multi-center validation", + author = "Weiskopf, Nikolaus and Suckling, John and Williams, Guy and + Correia, Marta M and Inkster, Becky and Tait, Roger and Ooi, Cinly + and Bullmore, Edward T and Lutti, Antoine", + journal = "Front. Neurosci.", + volume = 7, + pages = 95, + abstract = "Multi-center studies using magnetic resonance imaging facilitate + studying small effect sizes, global population variance and rare + diseases. The reliability and sensitivity of these multi-center + studies crucially depend on the comparability of the data + generated at different sites and time points. The level of + inter-site comparability is still controversial for conventional + anatomical T1-weighted MRI data. Quantitative multi-parameter + mapping (MPM) was designed to provide MR parameter measures that + are comparable across sites and time points, i.e., 1 mm + high-resolution maps of the longitudinal relaxation rate (R1 = + 1/T1), effective proton density (PD(*)), magnetization transfer + saturation (MT) and effective transverse relaxation rate (R2(*) = + 1/T2(*)). MPM was validated at 3T for use in multi-center studies + by scanning five volunteers at three different sites. We + determined the inter-site bias, inter-site and intra-site + coefficient of variation (CoV) for typical morphometric measures + [i.e., gray matter (GM) probability maps used in voxel-based + morphometry] and the four quantitative parameters. The inter-site + bias and CoV were smaller than 3.1 and 8\%, respectively, except + for the inter-site CoV of R2(*) (<20\%). The GM probability maps + based on the MT parameter maps had a 14\% higher inter-site + reproducibility than maps based on conventional T1-weighted + images. The low inter-site bias and variance in the parameters and + derived GM probability maps confirm the high comparability of the + quantitative maps across sites and time points. The reliability, + short acquisition time, high resolution and the detailed insights + into the brain microstructure provided by MPM makes it an + efficient tool for multi-center imaging studies.", + month = jun, + year = 2013, + keywords = "3T; MPM; MT; PD; T1; T2*; multi-center; qMRI", + language = "en" +} +,@ARTICLE{York2022-fl, + title = "Longitudinal microstructural {MRI} markers of demyelination and + neurodegeneration in early relapsing-remitting multiple sclerosis: + Magnetisation transfer, water diffusion and g-ratio", + author = "York, Elizabeth N and Meijboom, Rozanna and Thrippleton, Michael J + and Bastin, Mark E and Kampaite, Agniete and White, Nicole and + Chandran, Siddharthan and Waldman, Adam D", + journal = "NeuroImage: Clinical", + volume = 36, + pages = 103228, + abstract = "Introduction Quantitative microstructural MRI, such as + myelin-sensitive magnetisation transfer ratio (MTR) or saturation + (MTsat), axon-sensitive water diffusion Neurite Orientation + Dispersion and Density Imaging (NODDI), and the aggregate g-ratio, + may provide more specific markers of white matter integrity than + conventional MRI for early patient stratification in + relapsing-remitting multiple sclerosis (RRMS). The aim of this + study was to determine the sensitivity of such markers to + longitudinal pathological change within cerebral white matter + lesions (WML) and normal-appearing white matter (NAWM) in recently + diagnosed RRMS. Methods Seventy-nine people with recently + diagnosed RRMS, from the FutureMS longitudinal cohort, were + recruited to an extended MRI protocol at baseline and one year + later. Twelve healthy volunteers received the same MRI protocol, + repeated within two weeks. Ethics approval and written informed + consent were obtained. 3T MRI included magnetisation transfer, and + multi-shell diffusion-weighted imaging. NAWM and whole brain were + segmented from 3D T1-weighted MPRAGE, and WML from T2-weighted + FLAIR. MTR, MTsat, NODDI isotropic (ISOVF) and intracellular + (ICVF) volume fractions, and g-ratio (calculated from MTsat and + NODDI data) were measured within WML and NAWM. Brain parenchymal + fraction (BPF) was also calculated. Longitudinal change in BPF and + microstructural metrics was assessed with paired t-tests (α = + 0.05) and linear mixed models, adjusted for confounding factors + with False Discovery Rate (FDR) correction for multiple + comparisons. Longitudinal changes were compared with test-retest + Bland-Altman limits of agreement from healthy control white + matter. The influence of longitudinal change on g-ratio was + explored through post-hoc analysis in silico by computing g-ratio + with realistic simulated MTsat and NODDI values. Results In NAWM, + g-ratio and ICVF increased, and MTsat decreased over one year + (adjusted mean difference = 0.007, 0.005, and −0.057 respectively, + all FDR-corrected p < 0.05). There was no significant change in + MTR, ISOVF, or BPF. In WML, MTsat, NODDI ICVF and ISOVF increased + over time (adjusted mean difference = 0.083, 0.024 and 0.016, + respectively, all FDR-corrected p < 0.05). Group-level + longitudinal changes exceeded test-retest limits of agreement for + NODDI ISOVF and ICVF in WML only. In silico analysis showed + g-ratio may increase due to a decrease in MTsat or ISOVF, or an + increase in ICVF. Discussion G-ratio and MTsat changes in NAWM + over one year may indicate subtle myelin loss in early RRMS, which + were not apparent with BPF or NAWM MTR. Increases in NAWM and WML + NODDI ICVF were not anticipated, and raise the possibility of + axonal swelling or morphological change. Increases in WML MTsat + may reflect myelin repair. Changes in NODDI ISOVF are more likely + to reflect alterations in water content. Competing MTsat and ICVF + changes may account for the absence of g-ratio change in WML. + Longitudinal changes in microstructural measures are significant + at a group level, however detection in individual patients in + early RRMS is limited by technique reproducibility. Conclusion + MTsat and g-ratio are more sensitive than MTR to early + pathological changes in RRMS, but complex dependence of g-ratio on + NODDI parameters limit the interpretation of aggregate measures in + isolation. Improvements in technique reproducibility and + validation of MRI biophysical models across a range of + pathological tissue states are needed.", + month = jan, + year = 2022, + keywords = "Magnetization transfer imaging; MTsat; G-ratio; NODDI; + Diffusion-weighted imaging; Multiple sclerosis" +} +,@ARTICLE{Campbell2018-hi, + title = "Promise and pitfalls of g-ratio estimation with {MRI}", + author = "Campbell, Jennifer S W and Leppert, Ilana R and Narayanan, Sridar + and Boudreau, Mathieu and Duval, Tanguy and Cohen-Adad, Julien + and Pike, G Bruce and Stikov, Nikola", + journal = "Neuroimage", + publisher = "Elsevier BV", + volume = 182, + pages = "80--96", + abstract = "The fiber g-ratio is the ratio of the inner to the outer diameter + of the myelin sheath of a myelinated axon. It has a limited + dynamic range in healthy white matter, as it is optimized for + speed of signal conduction, cellular energetics, and spatial + constraints. In vivo imaging of the g-ratio in health and disease + would greatly increase our knowledge of the nervous system and + our ability to diagnose, monitor, and treat disease. MRI based + g-ratio imaging was first conceived in 2011, and expanded to be + feasible in full brain white matter with preliminary results in + 2013. This manuscript reviews the growing g-ratio imaging + literature and speculates on future applications. It details the + methodology for imaging the g-ratio with MRI, and describes the + known pitfalls and challenges in doing so.", + month = nov, + year = 2018, + keywords = "Diffusion MRI; MRI; Microstructure; Myelin imaging; White matter; + g-ratio", + language = "en" +} diff --git a/myst.yml b/myst.yml index 5068df8..47f06f7 100644 --- a/myst.yml +++ b/myst.yml @@ -74,6 +74,8 @@ project: - bibliography/afi.bib - bibliography/filtering.bib - bibliography/qmtchapter.bib + - bibliography/mtrchapter.bib + - bibliography/mtsatchapter.bib resources: - figures/2 T1 mapping/figure2-2.ipynb toc: