This tab runs simulations of pre-loaded pulse sequences at varying field strengths. Some pulse sequence parameters can be modified. The results of the simulations can be used by PINTS to produce simulated basis sets used for fitting spectra collected using ¹H-MRS.

• Simulation Options
  • Macromolecules
  • Pulse Sequences
    • semi-LASER (Siemens 3T/7T)
      • Pulse Shapes (7T)
      • Pulse Shapes (3T)
    • semi-LASER (Bruker 9.4T)
    • LASER (Varian 9.4T)
• Pulse Sequences and Calibration Parameters
  • semi-LASER (Siemens 3T/7T)
    • Automatic Sequence Calibration
  • semi-LASER (Bruker 9.4T)
    • Automatic Sequence Calibration
    • Glu/Gln Editing Pulse Parameters
  • LASER (Varian 9.4T)
    • Automatic Sequence Calibration
• Binning Options
• Running the Simulation
• Simulation Results

A brief description of each option is provided below.

• Field Strength: Simulations can be run for 7T, 3T, and 9.4T field strengths.
• Dwell Time: The time between sample points for a time domain signal.
• Acquisition Time: The time taken to acquire the time domain signal.
• Echo Time: The time from the start of the pulse sequence to the center of the recorded echo.
• PPM Range: The frequency range to be simulated.

You can add an empirically measured macromolecule model to the results of the simulation by selecting the "Include macromolecules in the simulation." option. Note that macromolecules in real life have a shorter T₂ than metabolites, so if you are using a long echo-time, it would not make physical sense to include a macromolecule model in your basis set.

Two macromolecule models are included with PINTS:

1. If you selected the 3T field strength, the model detailed in this paper will be included. In this paper, an experimentally acquired macromolecule baseline was collected using an inversion recovery sequence (TI = 750 ms) at 3T. The macromolecule baseline is shown below (Figure 2 in the paper):

2. If you selected the 7T or 9.4T field strength, the model detailed in this paper will be included. In this paper, an experimentally acquired macromolecule baseline was collected using an inversion recovery sequence at 7T detailed here. The macromolecule baseline is shown below (Figure 1 in the paper):

Currently, you can run simulations using three different sequences. Two are semi-LASER sequences, and one is a LASER sequence. Note that the simulations assume a perfectly homogeneous B₀ field and only simulate the RF pulses (does not account for gradient effects).

This is the semi-LASER sequence implemented on the 3T and 7T MRI machines at the Centre for Functional and Metabolic Mapping (CFMM) at the Robarts Research Institute (London, ON, Canada) and on the 3T MRI machines at St. Joseph's Health Care (London, ON, Canada).

In general, the semi-LASER sequence consists of an asymmetric 90-degree SLR-optimized sinc excitation pulse with two pairs of adiabatic refocussing pulses. The sequence is described in detail in this paper and is shown below (Figure 1 in the paper). Note that the VAPOR and OVS portion of the sequence is not simulated in PINTS.

Note that, for this sequence, different pulse shapes are used depending on the field strength selected.

If the "7 T (297.2 MHz)" option is selected, the following pulse shapes are used:

The 90-degree excitation pulse is shown on the left and the adiabatic full passage pulse is shown on the right. From top to bottom the real and imaginary parts of the pulse, the amplitude modulation function, and the frequency modulation function are shown, respectively.

These pulses are identical to the ones used on the 7T head-only MRI system at CFMM.

If the "3 T (123.3 MHz)" option is selected, the following pulse shapes are used:

The 90-degree excitation pulse is shown on the left and the adiabatic full passage pulse is shown on the right. From top to bottom the real and imaginary parts of the pulse, the amplitude modulation function, and the frequency modulation function are shown, respectively.

These pulses are identical to the ones used on the 3T hybrid PET/MRI system at St. Joseph's Health Care.

This is the semi-LASER sequence implemented on the 9.4T Bruker MRI machine at CFMM. The sequence is similar to the Siemens semi-LASER sequence. There is a 90-degree excitation pulse that is preceded by VAPOR / OVS and proceeded by two pairs of full-passage adiabatic refocusing pulses. Note that the VAPOR and OVS portion of the sequence is not simulated in PINTS. Gradients are also not simulated.

The sequence is shown below.

However, there are three major differences. The first is that the timings of the pulses are different. The delay between pulses are defined by two parameters: TE1 and TE2. The second is an editing pulse for glutamate and glutamine can be inserted in this sequence.

The third is that the pulse shapes for this sequence is different than the Siemens sequence. The following pulse shapes are used:

The 90-degree excitation pulse is shown on the left and the adiabatic full passage pulse is shown on the right. From top to bottom the real and imaginary parts of the pulse, the amplitude modulation function, and the frequency modulation function are shown, respectively.

This is the LASER sequence implemented on the (no longer available) 9.4T Varian MRI machine at CFMM. The sequence consists of one adiabatic half-passage pulse and six pairs of adiabatic full-passage pulses. Note that gradients are not simulated. The sequence is shown below and is described in more detail in this paper.

Here are the pulse shapes used for this sequence:

The adiabatic half passage pulse is shown on the left and the adiabatic full passage pulse is shown on the right. From top to bottom the real and imaginary parts of the pulse, the amplitude modulation function, and the frequency modulation function are shown, respectively.

You can adjust the simulation sequence parameters for the "semi-LASER (3T/7T)" sequence in the "semi-LASER (Siemens 3T/7T)" tab.

There are several pulse sequence parameter that can be adjusted:

• 90 Degree SLR Pulse Length: The length of the 90-degree excitation pulse in microseconds.
• 90 Degree SLR Fudge Factor: Option is deprecated, do not change.
• 180 Degree AFP Pulse Length: The length of the adiabatic full passage pulse in microseconds.
• RF Offset: This is equivalent to the centre frequency used on the scanner. This is typically the frequency of water (4.7 ppm).

PINTS will automatically calibrate the semi-LASER pulse strengths to ensure a proper 90-degree excitation occurs and that the adiabatic full passage pulses are of sufficient strength that they are operating in the adiabatic domain. Because the exact scanner environment is not replicated in the simulation, the pulse amplitudes that PINTS comes up with may not necessarily match the ones used on the scanner.

The semi-LASER sequence has several calibration parameters that can be adjusted:

• 90 Degree SLR Pulse Amplitudes (Minimum/Maximum): This sets the range of 90-degree pulse strengths that the program will calibrate over.
• 180 Degree AFP Pulse Amplitudes (Minimum/Maximum): This sets the range of adiabatic full passage pulse strengths that the program will calibrate over.
• Calibration Metabolite: The amplitude of this metabolite will be measured for to calibrate the pulses.

The calibration occurs as follows:

1. The sequence is run with an ideal 90 degree pulse while stepping up the pulse strength of the 180 degree AFP pulse. The amplitude of the calibration metabolite is recorded after each iteration of the pulse sequence is run.
2. The calibration metabolite amplitude vs. the AFP pulse strength is plotted and a sigmoid function is fitted to the curve (green = initial guess, red = final fit). Using the fitted function, an AFP pulse strength from the adiabatic region is chosen.
3. Using the calibrated AFP pulse strength, the sequence is run while stepping up the pulse strength of the 90-degree excitation pulse. Again, the amplitude of the calibration metabolite is recorded after each iteration of the pulse sequence is run.

4. The calibration metabolite amplitude vs. the 90-degree excitation pulse strength is plotted and a sine function is fitted to the curve (green = initial guess, red = final fit). Using the fitted function, the 90-degree excitation pulse strength is chosen to be the strength at which the peak of sinusoid occurs.

Unlike the "semi-LASER (Siemens 3T/7T)" sequence, for the "semi-LASER (Bruker 9.4T)" sequence, the parameters are automatically populated when you load a dataset acquired using this sequence from the Bruker scanner.

Load a dataset by using the browse button. Select the folder containing all the data from the acquisition. This folder should contain files such as acqp, fid, method, and others.

Then hit the load button. You'll notice that all the fields are populated with the appropriate parameters. Most parameters are unadjustable, but there are a some parameters that you can adjust:

• RF Offset: This is equivalent to the centre frequency used on the scanner. This is typically the frequency of water (4.7 ppm).
• DigShift: This is the number of sample points that the scanner requires to ramp up the acquisition gradient. You can adjust this value to indirectly add or subtract first-order phase in the simulated spectra. However, note that this is not typically something you'd want to do when generating a prior information template to fit an acquistion.

You can also adjust the calibration parameters and the editing pulse parameters.

Like with the "semi-LASER Siemens (3T/7T)" sequence, PINTS will automatically calibrate the semi-LASER pulse strengths to ensure a proper 90-degree excitation occurs and that the adiabatic full passage pulses are of sufficient strength that they are operating in the adiabatic domain. More details about the calibration parameters that you can adjust and how the automatic sequence calibration works is given above. Examples of the adiabatic full passage calibration and the excitation pulse calibration for the "semi-LASER (Bruker 9.4T) sequence" is given below.

(Addition of the glutamate/glutamine editing pulse to this sequence is coming in the next update of the software)

The LASER sequence has several pulse sequence parameters that can be adjusted in the "LASER (Varian 9.4T)" tab:

• AHP Pulse Length: The length of the adiabatic half passage pulse in microseconds.
• AFP Pulse Length: The length of the adiabatic full passage pulse in microseconds.
• RF Offset: This is equivalent to the centre frequency used on the scanner. This is typically the frequency of water (4.7 ppm).

PINTS will automatically calibrate the semi-LASER pulse strengths to ensure a proper 90-degree excitation occurs and that the adiabatic full passage pulses are of sufficient strength that they are operating in the adiabatic domain. Because the exact scanner environment is not replicated in the simulation, the pulse amplitudes that PINTS comes up with may not necessarily match the ones used on the scanner.

The semi-LASER sequence has several calibration parameters that can be adjusted:

• 90 Degree SLR Pulse Amplitudes (Minimum/Maximum): This sets the range of 90-degree pulse strengths that the program will calibrate over.
• 180 Degree AFP Pulse Amplitudes (Minimum/Maximum): This sets the range of adiabatic full passage pulse strengths that the program will calibrate over.
• Calibration Metabolite: The amplitude of this metabolite will be measured for to calibrate the pulses.

The calibration occurs as follows:

1. The sequence is run with an ideal 90 degree pulse while stepping up the pulse strength of the 180 degree AFP pulse. The amplitude of the calibration metabolite is recorded after each iteration of the pulse sequence is run.
2. The calibration metabolite amplitude vs. the AFP pulse strength is plotted and a sigmoid function is fitted to the curve (green = initial guess, red = final fit). Using the fitted function, an AFP pulse strength from the adiabatic region is chosen.
3. Using the calibrated AFP pulse strength, the sequence is run while stepping up the pulse strength of the adiabatic half passage pulse. Again, the amplitude of the calibration metabolite is recorded after each iteration of the pulse sequence is run.

4. The calibration metabolite amplitude vs. the adiabatic half passage pulse strength is plotted and a sigmoid function is fitted to the curve (green = initial guess, red = final fit). Using the fitted function, an AHP pulse strength from the adiabatic region is chosen.

A binning process is used after the simulations are complete to remove degenerate peaks from the output. PINTS uses the PyGamma Library as a back end to do the simulations and the transition tables calculated by the GAMMA density matrix simulations frequently contain a large number of transitions caused by degenerate splittings and other processes.

At the conclusion of each simulation run a routine is called to extract lines from the transition table. These lines are then normalized using a closed form calculation based on the number of spins. To reduce the number of lines required for display, multiple lines are blended by binning them together based on their PPM locations and phases. The following parameters can be used to customize these procedures:

• Peak Search Range, Low/High (PPM): the range in PPM that is searched for lines from the metabolite simulation.
• Peak Blending Tolerance (PPM and Degrees): the width of the bins (+/- in PPM and +/- in Phase Degrees) that are used to blend the lines in the simulation. Lines that are included in the same bin are summed using complex addition based on Amplitude and Phase.

This is easy! Hit the "Confirm Simulation Parameters" button. Some information about the simulation you are about to run will appear in the "Simulation Console." This is your opportunity to tweak any simulation parameters if you want. Once you are happy with the options you have, hit the "Run Simulation" button. The program will simulate up to 4 metabolites in parallel.

Simulation results are automatically saved to the pints/experiments/<pulse sequence>_<date>_<time stamp>_TE<echo-time>_<b0>T folder. In this folder you will find:

• Two *.png files that show your pulse shapes.
• Two *.pdf files that show your calibration results.
• console.txt which contains the Simulation Console output.
• <sequence>_sim_results.txt which contains the results of the simulation. This file can be loaded back into PINTS and be used to generate a FITMAN compatible *.cst and *.ges files.